Genetic markers for Alzheimer's disease and methods using the same

• US 20030170678A1
• Filed: 10/25/2002
• Published: 09/11/2003
• Est. Priority Date: 10/25/2001
• Status: Abandoned Application

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: TorreyPines Therapeutics, Inc. /Old/
• Inventors: Blacker, Deborah Lynne, Wang, Xin, Velicelebi, Gonul, Bertram, Lars, Tanzi, Rudolph E., Elliott, Kathryn J., Saunders, Aleister J., Becker, Kenneth David
• Application Number:
  US10/281,456
• Publication Number:
  US 20030170678A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers

Abstract

Genetic markers associated with Alzheimer'"'"'s disease are provided. Also provided are methods of determining the presence or absence in a subject of one or more polymorphisms associated with Alzheimer'"'"'s disease and methods of determining the level of risk for Alzheimer'"'"'s disease in a subject. Further provided are nucleic acid compositions and kits for use in determining the presence or absence in a subject of one or more polymorphisms associated with Alzheimer'"'"'s disease and kits for determining the level of risk for Alzheimer'"'"'s disease in a subject.

Claims

1. A method for detecting the presence or absence in a subject of a polymorphism associated with Alzheimer'"'"'s disease, comprising analyzing chromosome 10 of the subject for a polymorphism associated with Alzheimer'"'"'s disease.

2. The method of claim 1, wherein the polymorphism is on chromosome 10q.

3. The method of claim 1, wherein the polymorphism is located on chromosome 10q22, 10q23, 10q24, 10q25 or 10q26.

4. The method of claim 1, wherein the polymorphism is located in a region of chromosome 10 about 30 cM around and including D10S583, or about 20 cM around and including D10S583, or about 15 cM around and including D10S583, or about 12 cM around and including D10S583, or about 10 cM around and including D10S583.

5. The method of claim 1, wherein the polymorphism is located in a region of chromosome 10 about 5 cM around and including D10S583, or about 4 cM around and including D10S583, or about 3 cM around and including D10S583, or about 2 cM around D10S583, or about 1 cM around and including D10S583, or about 0.5 cM around and including D10S583, or about 0.25 cM around and including D10S583, or about 0.1 cM around and including D10S583.

6. The method of claim 1, wherein the polymorphism is located in a region of chromosome 10 about 30 Mb around and including D10S583, or about 28 Mb around and including D10S583, or about 20 Mb around and including D10S583, or about 15 Mb around and including D10S583, or about 10 Mb around and including D10S583, or about 5 Mb around and including D10S583, or about 2.5 Mb around and including D10S583, or about 1 Mb around and including D10S583 or about 500 kb around and including D10S583, or about 200 kb around and including D10S583, or about 100 kb around and including D10S583, or about 50 kb around and including D10S583, or about 40 kb around and including D10S583, or about 20 kb around and including D10S583, or about 10 kb around and including D10S583, or about 5 kb around and including D10S583, or about 1 kb around and including D10S583.

7. The method of claim 1, wherein the polymorphism is located in one or more of the following regions of chromosome 10:

(a) the region extending about 50 cM, or about 45 cM, or about 33 cM, or about 30 cM, or about 25 cM, or about 21 cM, or about 15 cM, or about 10 cM, or about 5 cM, or about 4 cM, or about 3 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 60 cM, or about 55 cM, or about 50 cM, or about 45 cM, or about 40 cM, or about 35 cM, or about 30 cM, or about 25 cM, or about 20 cM, or about 15 cM, or about 13 cM, or about 12 cM, or about 9 cM, or about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending from and including marker D10S583 to the terminus of the q arm of chromosome 10,

(d) the region extending from and including marker D10S583 to the centromere of chromosome 10,

(e) the region extending about 62 Mb, about 55 Mb, or about 50 Mb, or about 32 Mb, or about 28 Mb, or about 25 Mb, or about 20 Mb, or about 15 Mb, or about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb proximal from and including marker D10S583,

(f) the region extending about 45 Mb, or about 40 Mb, or about 35 Mb, or about 30 Mb, or about 25 Mb, or about 20 Mb, or about 16 Mb, or about 14 Mb, or about 13 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb distal from and including marker D10S583,

(g) the region between D10S564 and D10S583, inclusive,

(h) the region between D10S583 and D10S1710, inclusive,

(i) the region between D10S583 and D10S566, inclusive,

(j) the region between D10S583 and D10S1671, inclusive and

(k) the region between D10S583 and D10S1741, inclusive.

8. The method of claim 1, wherein the polymorphism is located in one or more of the following regions of chromosome 10:

(a) the region extending about 5 cM, or about 4 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 80 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb proximal from and including marker D10S583; and

(d) the region extending about 10 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb distal from and including marker D10S583.

9. The method of claim 1, wherein the polymorphism is an allele of D10S583.

11. The method of claim 1, wherein the polymorphism is associated with AD with onset ages of greater than or equal to about 50 years, or greater than or equal to about 60 years, or greater than or equal to about 65 years.

12. The method of claim 1, wherein the polymorphism is associated with an AD DNA segment that has an effect size comparable to or greater than the effect size of APOE.

13. The method of claim 1, wherein the polymorphism is located within an AD DNA segment.

14. The method of claim 1, wherein the association between the polymorphism and Alzheimer'"'"'s disease is such that it yields a positive result in a family-based test for association.

15. The method of claim 14, wherein the positive result is a P value less than or equal to 0.05.

16. The method of claim 14, wherein the positive result is a P value less than 0.05.

32. The method of claim 1, wherein the polymorphism is located on chromosome 10q22, 10q23 or 10q24.

35. The method of claim 1, wherein the polymorphism is located about 30 Mb around and including D10S583, or about 28 Mb around and including D10S583, or about 20 Mb around and including D10S583, or about 15 Mb around and including D10S583, or about 10 Mb around and including D10S583.

36. The method of claim 1, wherein the polymorphism is located about 5 Mb around and including D10S583, or about 2.5 Mb around and including D10S583, or about 1 Mb around and including D10S583 or about 500 kb around and including D10S583, or about 200 kb around and including D10S583, or about 100 kb around and including D10S583, or about 50 kb around and including D10S583, or about 40 kb around and including D10S583, or about 20 kb around and including D10S583, or about 10 kb around and including D10S583, or about 5 kb around and including D10S583, or about 1 kb around and including D10S583.

97. The method of claim 1, wherein the polymorphism is associated with an AD gene that accounts for greater than 1% of the attributtable risk of AD.

98. The method of claim 1, wherein the polymorphism is associated with an AD gene that accounts for greater than 2% of the attributtable risk of AD.

99. The method of claim 1, wherein the polymorphism is associated with an AD gene that accounts for greater than 5% of the attributtable risk of AD.

100. The method of claim 1, wherein the polymorphism is associated with an AD gene that accounts for greater than 10% of the attributtable risk of AD.

101. The method of claim 1, wherein the polymorphism is associated with an AD gene that accounts for greater than 25% of the attributtable risk of AD.

112. The method of claim 1, wherein the polymorphism is located on chromosome 10q23, 10q24 or 10q25.

114. The method of claim 1, wherein the polymorphism is located within the PLAU gene.

115. The method of claim 1, wherein the polymorphism is located within the TLL2 gene.

116. The method of claim 1, wherein the polymorphism is located within the PSAP gene.

117. The method of claim 1, wherein the polymorphism is located within the PSD gene.

118. The method of claim 7, wherein the polymorphism is located within the KIAA0904 gene.

119. The method of claim 1, wherein the polymorphism is located within the NFKB2 gene.

120. The method of claim 1, wherein the polymorphism is located within the PPP3CB gene.

121. The method of claim 1, wherein the polymorphism is located within the CH25H gene.

122. The method of claim 1, wherein the polymorphism is located within the FERIL3 gene.

175. The method of claim 1, wherein the polymorphism is associated with AD with onset ages of greater than or equal to about 65 years.

245. The method of any of claims 1, 17, 18, 28, 39, 59, or 135, wherein the polymorphism is located in a region of chromosome 10 about 1 Mb around and including D10S583, or about 500 kb around and including D10S583, or about 200 kb around and including D10S583, or about 100 kb around and including D10S583, or about 50 kb around and including D10S583, or about 40 kb around and including D10S583, or about 20 kb around and including D10S583, or about 10 kb around and including D10S583, or about 5 kb around and including D10S583, or about 1 kb around and including D10S583.

246. The method of any of claims 1, 17, 18, 28, 39, 59, or 135, wherein the polymorphism is located in a region of chromosome 10 about 0.3 Mb around and including D10S583, or about 0.2 Mb around and including D10S583, or about 0.2 Mb around and including D10S583.

247. The method of any of claims 1, 17, 18, 28, 39, 59, or 135, wherein the polymorphism is located in the region of chromosome 10 extending about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb proximal from and including marker D10S583.

248. The method of any of claims 1, 17, 18, 28, 39, 59, or 135, wherein the polymorphism is located in the region of chromosome 10 extending about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb distal from and including marker D10S583.

249. The method of any of claims 1, 17, 18, 28, 39, 59, or 135, wherein the polymorphism is located in a region of chromosome 10 about 1 cM around and including D10S583, or about 0.5 cM around and including D10S583, or about 0.25 cM around and including D10S583, or about 0.1 cM around and including D10S583.

250. The method of any of claims 1, 17, 18, 28, 39, 59, or 135, wherein the polymorphism is located in the region of chromosome 10 extending about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583.

251. The method of any of claims 1, 17, 18, 28, 39, 59, or 135, wherein the polymorphism is located in the region of chromosome 10 extending about 1 cM, or about 0.5 cM, or about 0.1 cM distal (telomeric) from and including marker D10S583.

10. A method for detecting the presence or absence in a subject of two or more polymorphisms associated with Alzheimer'"'"'s disease, comprising analyzing chromosome 10 of the subject for two or more polymorphisms associated with Alzheimer'"'"'s disease, wherein at least one polymorphism is an allele of D10S583.

176. The method of claim 10, wherein the two or more polymorphisms are located on chromosome 10q.

177. The method of claim 10, wherein each of the two or more polymorphisms is located on chromosome 10q22, 10q23 or 10q24.

178. The method of claim 10, wherein each of the two or more polymorphisms is located on chromosome 10q23, 10q24 or 10q25.

179. The method of claim 10, wherein each of the two or more polymorphisms is located in a region of chromosome 10 about 30 cM around and including D10S583, or about 20 cM around and including D10S583, or about 15 cM around and including D10S583, or about 12 cM around and including D10S583, or about 10 cM around and including D10S583.

180. The method of claim 10, wherein each of the two or more polymorphisms is located in a region of chromosome 10 about 5 cM around and including D10S583, or about 4 cM around and including D10S583, or about 3 cM around and including D10S583, or about 2 cM around D10S583, or about 1 cM around and including D10S583, or about 0.5 cM around and including D10S583, or about 0.25 cM around and including D10S583, or about 0.1 cM around and including D10S583.

181. The method of claim 10, wherein each of the two or more polymorphisms is located in a region of chromosome 10 about 30 Mb around and including D10S583, or about 28 Mb around and including D10S583, or about 20 Mb around and including D10S583, or about 15 Mb around and including D10S583, or about 10 Mb around and including D10S583.

182. The method of claim 10, wherein each of the two or more polymorphisms is located in a region of chromosome 10 about 5 Mb around and including D10S583, or about 2.5 Mb around and including D10S583, or about 1 Mb around and including D10S583 or about 500 kb around and including D10S583, or about 200 kb around and including D10S583, or about 100 kb around and including D10S583, or about 50 kb around and including D10S583, or about 40 kb around and including D10S583, or about 20 kb around and including D10S583, or about 10 kb around and including D10S583, or about 5 kb around and including D10S583, or about 1 kb around and including D10S583.

183. The method of claim 10, wherein each of the two or more polymorphisms is located one or more of the following regions of chromosome 10:

(a) the region extending about 50 cM, or about 45 cM, or about 33 cM, or about 30 cM, or about 25 cM, or about 21 cM, or about 15 cM, or about 10 cM, or about 5 cM, or about 4 cM, or about 3 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 60 cM, or about 55 cM, or about 50 cM, or about 45 cM, or about 40 cM, or about 35 cM, or about 30 cM, or about 25 cM, or about 20 cM, or about 15 cM, or about 13 cM, or about 12 cM, or about 9 cM, or about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending from and including marker D10S583 to the terminus of the q arm of chromosome 10,

(d) the region extending from and including marker D10S583 to the centromere of chromosome 10,

(e) the region extending about 62 Mb, about 55 Mb, or about 50 Mb, or about 32 Mb, or about 28 Mb, or about 25 Mb, or about 20 Mb, or about 15 Mb, or about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb proximal from and including marker D10S583,

(f) the region extending about 45 Mb, or about 40 Mb, or about 35 Mb, or about 30 Mb, or about 25 Mb, or about 20 Mb, or about 16 Mb, or about 14 Mb, or about 13 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb distal from and including marker D10S583,

(g) the region between D10S564 and D10S583, inclusive,

(h) the region between D10S583 and D10S1710, inclusive,

(i) the region between D10S583 and D10S566, inclusive,

(j) the region between D10S583 and D10S1671, inclusive and

(k) the region between D10S583 and D10S1741, inclusive.

184. The method of claim 10, wherein each of the two or more polymorphisms is located one or more of the following regions of chromosome 10:

(a) the region extending about 5 cM, or about 4 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 80 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb proximal from and including marker D10S583; and

(d) the region extending about 10 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb distal from and including marker D10S583.

185. The method of claim 10, wherein each of the two or more polymorphisms is located on chromosome 10q22, 10q23, 10q24, 10q25 or 10q26.

17. A method for indicating a predisposition to or the occurrence of Alzheimer'"'"'s disease in a subject, comprising:

detecting in nucleic acid obtained from the subject the presence or absence of a polymorphism on chromosome 10 associated with Alzheimer'"'"'s disease, wherein the presence of the polymorphism is indicative of a predisposition to Alzheimer'"'"'s disease.

19. The method of claim 17, wherein the polymorphism is located on chromosome 10q.

20. The method of claim 17, wherein the polymorphism is located on chromosome 10q22, 10q23, 10q24, 10q25 or 10q26.

21. The method of claim 17, wherein the polymorphism is located on chromosome 10q22, 10q23 or 10q24.

22. The method of claim 17, wherein the polymorphism is located in a region of chromosome 10 selected from the group consisting of:

(a) the region extending about 50 cM, or about 45 cM, or about 33 cM, or about 30 cM, or about 25 cM, or about 21 cM, or about 15 cM, or about 10 cM, or about 5 cM, or about 4 cM, or about 3 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 60 cM, or about 55 cM, or about 50 cM, or about 45 cM, or about 40 cM, or about 35 cM, or about 30 cM, or about 25 cM, or about 20 cM, or about 15 cM, or about 13 cM, or about 12 cM, or about 9 cM, or about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending from and including marker D10S583 to the terminus of the q arm of chromosome 10,

(d) the region extending from and including marker D10S583 to the centromere of chromosome 10,

(e) the region extending about 62 Mb, about 55 Mb, or about 50 Mb, or about 32 Mb, or about 28 Mb, or about 25 Mb, or about 20 Mb, or about 15 Mb, or about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb proximal from and including marker D10S583,

(f) the region extending about 45 Mb, or about 40 Mb, or about 35 Mb, or about 30 Mb, or about 25 Mb, or about 20 Mb, or about 16 Mb, or about 14 Mb, or about 13 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb distal from and including marker D10S583,

(g) the region between D10S564 and D10S583, inclusive,

(h) the region between D10S583 and D10S1710, inclusive,

(i) the region between D10S583 and D10S566, inclusive,

(j) the region between D10S583 and D10S1671, inclusive and

(k) the region between D10S583 and D10S1741, inclusive.

23. The method of claim 17, wherein the polymorphism is located in a region of chromosome 10 selected from the group consisting of:

(a) the region extending about 5 cM, or about 4 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 80 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb proximal from and including marker D10S583; and

(d) the region extending about 10 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb distal from and including marker D10S583.

24. The method of claim 17, wherein the polymorphism is located about 30 cM around and including D10S583, or about 20 cM around and including D10S583, or about 15 cM around and including D10S583, or about 12 cM around and including D10S583, or about 10 cM around and including D10S583.

25. The method of claim 17, wherein the polymorphism is located about 5 cM around and including D10S583, or about 4 cM around and including D10S583, or about 3 cM around and including D10S583, or about 2 cM around D10S583, or about 1 cM around and including D10S583, or about 0.5 cM around and including D10S583, or about 0.25 cM around and including D10S583, or about 0.1 cM around and including D10S583.

26. The method of claim 17, wherein the polymorphism is located about 30 Mb around and including D10S583, or about 28 Mb around and including D10S583, or about 20 Mb around and including D10S583, or about 15 Mb around and including D10S583, or about 10 Mb around and including D10S583.

27. The method of claim 17, wherein the polymorphism is located about 5 Mb around and including D10S583, or about 2.5 Mb around and including D10S583, or about 1 Mb around and including D10S583 or about 500 kb around and including D10S583, or about 200 kb around and including D10S583, or about 100 kb around and including D10S583, or about 50 kb around and including D10S583, or about 40 kb around and including D10S583, or about 20 kb around and including D10S583, or about 10 kb around and including D10S583, or about 5 kb around and including D10S583, or about 1 kb around and including D10S583.

123. The method of claim 17, wherein the polymorphism is located within the PLAU gene.

186. The method of claim 17, wherein the polymorphism is located on chromosome 10q23, 10q24 or 10q25.

192. The method of claim 17, wherein the polymorphism is located within the TLL2 gene.

193. The method of claim 17, wherein the polymorphism is located within the PSAP gene.

194. The method of claim 17, wherein the polymorphism is located within the PSD gene.

195. The method of claim 17, wherein the polymorphism is located within the KIAA0904 gene.

196. The method of claim 17, wherein the polymorphism is located within the NFKB2 gene.

197. The method of claim 17, wherein the polymorphism is located within the PPP3CB gene.

198. The method of claim 17, wherein the polymorphism is located within the CH25H gene.

199. The method of claim 17, wherein the polymorphism is located within the FERIL3 gene.

18. A method for confirming a phenotypic diagnosis of Alzheimer'"'"'s disease in a subject, comprising:

detecting in nucleic acid obtained from the subject the presence or absence of a polymorphism on chromosome 10 associated with Alzheimer'"'"'s disease, wherein the presence of the polymorphism confirms a phenotypic diagnosis of Alzheimer'"'"'s disease.

187. The method of claim 18, wherein the polymorphism is located on chromosome 10q23, 10q24 or 10q25.

200. The method of claim 18, wherein the polymorphism is located within the PLAU gene.

201. The method of claim 18, wherein the polymorphism is located within the TLL2 gene.

202. The method of claim 18, wherein the polymorphism is located within the PSAP gene.

203. The method of claim 18, wherein the polymorphism is located within the PSD gene.

204. The method of claim 18, wherein the polymorphism is located within the KIAA0904 gene.

205. The method of claim 18, wherein the polymorphism is located within the NFKB2 gene.

206. The method of claim 18, wherein the polymorphism is located within the PPP3CB gene.

207. The method of claim 18, wherein the polymorphism is located within the CH25H gene.

208. The method of claim 18, wherein the polymorphism is located within the FERIL3 gene.

28. A method for predicting a response of a subject to a drug used to treat Alzheimer'"'"'s disease, comprising:

detecting the presence or absence of at least one polymorphism on chromosome 10 associated with Alzheimer'"'"'s disease, wherein the presence of the polymorphism is indicative of an increased or decreased likelihood that the drug treatment for Alzheimer'"'"'s disease will be effective.

29. The method of claim 28, wherein the polymorphism is located on chromosome 10q.

30. The method of claim 28, wherein the polymorphism is located on chromosome 10q22, 10q23, 10q24, 10q25 or 10q26.

31. The method of claim 28, wherein the polymorphism is located on chromosome 10q22, 10q23 or 10q24.

33. The method of claim 28, wherein the polymorphism is located about 30 cM around and including D10S583, or about 20 cM around and including D10S583, or about 15 cM around and including D10S583, or about 12 cM around and including D10S583, or about 10 cM around and including D10S583.

34. The method of claim 28, wherein the polymorphism is located about 5 cM around and including D10S583, or about 4 cM around and including D10S583, or about 3 cM around and including D10S583, or about 2 cM around D10S583, or about 1 cM around and including D10S583, or about 0.5 cM around and including D10S583, or about 0.25 cM around and including D10S583, or about 0.1 cM around and including D10S583.

37. The method of claim 28, wherein the polymorphism is located in a region of chromosome 10 selected from the group consisting of:

(a) the region extending about 50 cM, or about 45 cM, or about 33 cM, or about 30 cM, or about 25 cM, or about 21 cM, or about 15 cM, or about 10 cM, or about 5 cM, or about 4 cM, or about 3 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 60 cM, or about 55 cM, or about 50 cM, or about 45 cM, or about 40 cM, or about 35 cM, or about 30 cM, or about 25 cM, or about 20 cM, or about 15 cM, or about 13 cM, or about 12 cM, or about 9 cM, or about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending from and including marker D10S583 to the terminus of the q arm of chromosome 10,

(d) the region extending from and including marker D10S583 to the centromere of chromosome 10,

(e) the region extending about 62 Mb, about 55 Mb, or about 50 Mb, or about 32 Mb, or about 28 Mb, or about 25 Mb, or about 20 Mb, or about 15 Mb, or about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb proximal from and including marker D10S583,

(f) the region extending about 45 Mb, or about 40 Mb, or about 35 Mb, or about 30 Mb, or about 25 Mb, or about 20 Mb, or about 16 Mb, or about 14 Mb, or about 13 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb distal from and including marker D10S583,

(g) the region between D10S564 and D10S583, inclusive,

(h) the region between D10S583 and D10S1710, inclusive,

(i) the region between D10S583 and D10S566, inclusive,

(j) the region between D10S583 and D10S1671, inclusive and

(k) the region between D10S583 and D10S1741, inclusive.

38. The method of claim 28, wherein the polymorphism is located in a region of chromosome 10 selected from the group consisting of:

(a) the region extending about 5 cM, or about 4 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 80 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb proximal from and including marker D10S583; and

(d) the region extending about 10 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb distal from and including marker D10S583.

188. The method of claim 28, wherein the polymorphism is located on chromosome 10q23, 10q24 or 10q25.

209. The method of claim 28, wherein the polymorphism is located within the PLAU gene.

210. The method of claim 28, wherein the polymorphism is located within the TLL2 gene.

211. The method of claim 28, wherein the polymorphism is located within the PSAP gene.

212. The method of claim 28, wherein the polymorphism is located within the PSD gene.

213. The method of claim 28, wherein the polymorphism is located within the KIAA0904 gene.

214. The method of claim 28, wherein the polymorphism is located within the NFKB2 gene.

215. The method of claim 28, wherein the polymorphism is located within the PPP3CB gene.

216. The method of claim 28, wherein the polymorphism is located within the CH25H gene.

217. The method of claim 28, wherein the polymorphism is located within the FERIL3 gene.

39. A method of treating a subject manifesting an Alzheimer'"'"'s disease phenotype, comprising:

detecting in nucleic acid obtained from the subject the presence of a polymorphism on chromosome 10 associated with Alzheimer'"'"'s disease, wherein the presence of the polymorphism is indicative of the occurrence of Alzheimer'"'"'s disease in a subject; and

selecting and administering a treatment that is effective for treatment of Alzheimer'"'"'s disease.

40. The method of claim 39, wherein the polymorphism is located on chromosome 10q.

41. The method of claim 39, wherein the polymorphism is located on chromosome 10q22, 10q23, 10q24, 10q25 or 10q26.

42. The method of claim 39, wherein the polymorphism is located on chromosome 10q22, 10q23 or 10q24.

43. The method of claim 39, wherein the polymorphism is located about 30 cM around and including D10S583, or about 20 cM around and including D10S583, or about 15 cM around and including D10S583, or about 12 cM around and including D10S583, or about 10 cM around and including D10S583.

44. The method of claim 39, wherein the polymorphism is located about 5 cM around and including D10S583, or about 4 cM around and including D10S583, or about 3 cM around and including D10S583, or about 2 cM around D10S583, or about 1 cM around and including D10S583, or about 0.5 cM around and including D10S583, or about 0.25 cM around and including D10S583, or about 0.1 cM around and including D10S583.

45. The method of claim 39, wherein the polymorphism is located about 30 Mb around and including D10S583, or about 28 Mb around and including D10S583, or about 20 Mb around and including D10S583, or about 15 Mb around and including D10S583, or about 10 Mb around and including D10S583.

46. The method of claim 39, wherein the polymorphism is located about 5 Mb around and including D10S583, or about 2.5 Mb around and including D10S583, or about 1 Mb around and including D10S583 or about 500 kb around and including D10S583, or about 200 kb around and including D10S583, or about 100 kb around and including D10S583, or about 50 kb around and including D10S583, or about 40 kb around and including D10S583, or about 20 kb around and including D10S583, or about 10 kb around and including D10S583, or about 5 kb around and including D10S583, or about 1 kb around and including D10S583.

47. The method of claim 39, wherein the polymorphism is located in a region of chromosome 10 selected from the group consisting of:

(a) the region extending about 50 cM, or about 45 cM, or about 33 cM, or about 30 cM, or about 25 cM, or about 21 cM, or about 15 cM, or about 10 cM, or about 5 cM, or about 4 cM, or about 3 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 60 cM, or about 55 cM, or about 50 cM, or about 45 cM, or about 40 cM, or about 35 cM, or about 30 cM, or about 25 cM, or about 20 cM, or about 15 cM, or about 13 cM, or about 12 cM, or about 9 cM, or about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending from and including marker D10S583 to the terminus of the q arm of chromosome 10,

(d) the region extending from and including marker D10S583 to the centromere of chromosome 10,

(e) the region extending about 62 Mb, about 55 Mb, or about 50 Mb, or about 32 Mb, or about 28 Mb, or about 25 Mb, or about 20 Mb, or about 15 Mb, or about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb proximal from and including marker D10S583,

(f) the region extending about 45 Mb, or about 40 Mb, or about 35 Mb, or about 30 Mb, or about 25 Mb, or about 20 Mb, or about 16 Mb, or about 14 Mb, or about 13 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb distal from and including marker D10S583,

(g) the region between D10S564 and D10S583, inclusive,

(h) the region between D10S583 and D10S1710, inclusive,

(i) the region between D10S583 and D10S566, inclusive,

(j) the region between D10S583 and D10S1671, inclusive and

(k) the region between D10S583 and D10S1741, inclusive.

48. The method of claim 39, wherein the polymorphism is located in a region of chromosome 10 selected from the group consisting of:

(a) the region extending about 5 cM, or about 4 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 80 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb proximal from and including marker D10S583; and

(d) the region extending about 10 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb distal from and including marker D10S583.

189. The method of claim 39, wherein the polymorphism is located on chromosome 10q23, 10q24 or 10q25.

218. The method of claim 39, wherein the polymorphism is located within the PLAU gene.

219. The method of claim 39, wherein the polymorphism is located within the TLL2 gene.

220. The method of claim 39, wherein the polymorphism is located within the PSAP gene.

221. The method of claim 39, wherein the polymorphism is located within the PSD gene.

222. The method of claim 39, wherein the polymorphism is located within the KIAA0904 gene.

223. The method of claim 39, wherein the polymorphism is located within the NFKB2 gene.

224. The method of claim 39, wherein the polymorphism is located within the PPP3CB gene.

225. The method of claim 39, wherein the polymorphism is located within the CH25H gene.

226. The method of claim 39, wherein the polymorphism is located within the FERIL3 gene.

49. A method for identifying a gene as a candidate Alzheimer'"'"'s disease gene, comprising selecting a gene on chromosome 10q that is or encodes a product that has one or more properties which relate to one or more phenomena in neurodegenerative disease and thereby identifying a candidate Alzheimer'"'"'s disease gene.

50. The method of claim 49, wherein the gene is on chromosome 10q22, 10q23, 10q24, 10q25 or 10q26.

51. The method of claim 49, wherein the gene is on chromosome 10q22, 10q23 or 10q24.

52. The method of claim 49, wherein the gene on chromosome 10q is located about 30 cM around and including D10S583, or about 20 cM around and including D10S583, or about 15 cM around and including D10S583, or about 12 cM around and including D10S583, or about 10 cM around and including D10S583.

53. The method of claim 49, wherein the gene on chromosome 10 is located about 5 cM around and including D10S583, or about 4 cM around and including D10S583, or about 3 cM around and including D10S583, or about 2 cM around D10S583, or about 1 cM around and including D10S583, or about 0.5 cM around and including D10S583, or about 0.25 cM around and including D10S583, or about 0.1 cM around and including D10S583.

54. The method of claim 49, wherein the gene on chromosome 10 is located about 30 Mb around and including D10S583, or about 28 Mb around and including D10S583, or about 20 Mb around and including D10S583, or about 15 Mb around and including D10S583, or about 10 Mb around and including D10S583.

55. The method of claim 49, wherein the gene on chromsome 10 is located about 5 Mb around and including D10S583, or about 2.5 Mb around and including D10S583, or about 1 Mb around and including D10S583 or about 500 kb around and including D10S583, or about 200 kb around and including D10S583, or about 100 kb around and including D10S583, or about 50 kb around and including D10S583, or about 40 kb around and including D10S583, or about 20 kb around and including D10S583, or about 10 kb around and including D10S583, or about 5 kb around and including D10S583, or about 1 kb around and including D10S583.

56. The method of claim 49, wherein the gene on chromosome 10 is located in a region of chromosome 10 selected from the group consisting of:

(a) the region extending about 50 cM, or about 45 cM, or about 33 cM, or about 30 cM, or about 25 cM, or about 21 cM, or about 15 cM, or about 10 cM, or about 5 cM, or about 4 cM, or about 3 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 60 cM, or about 55 cM, or about 50 cM, or about 45 cM, or about 40 cM, or about 35 cM, or about 30 cM, or about 25 cM, or about 20 cM, or about 15 cM, or about 13 cM, or about 12 cM, or about 9 cM, or about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending from and including marker D10S583 to the terminus of the q arm of chromosome 10,

(d) the region extending from and including marker D10S583 to the centromere of chromosome 10,

(e) the region extending about 62 Mb, about 55 Mb, or about 50 Mb, or about 32 Mb, or about 28 Mb, or about 25 Mb, or about 20 Mb, or about 15 Mb, or about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb proximal from and including marker D10S583,

(f) the region extending about 45 Mb, or about 40 Mb, or about 35 Mb, or about 30 Mb, or about 25 Mb, or about 20 Mb, or about 16 Mb, or about 14 Mb, or about 13 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb distal from and including marker D10S583,

(g) the region between D10S564 and D10S583, inclusive,

(h) the region between D10S583 and D10S1710, inclusive,

(i) the region between D10S583 and D10S566, inclusive,

(j) the region between D10S583 and D10S1671, inclusive and

(k) the region between D10S583 and D10S1741, inclusive.

57. The method of claim 49, wherein the gene on chromosome 10 is located in a region of chromosome 10 selected from the group consisting of:

(a) the region extending about 5 cM, or about 4 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 80 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb proximal from and including marker D10S583; and

(d) the region extending about 10 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb distal from and including marker D10S583.

58. The method of claim 49, wherein the one or more phenomena in neurodegenerative disease is selected from the group consisting of senile plaques and components thereof, neuritic plaques, and components thereof, neurofibrillary tangles, tau protein, abnormally phosphorylated tau protein, amyloid precursor protein (APP), processing of APP, Aβ

42 protein, α

-, β

- and γ

-secretases, presenilin proteins, amyloid deposition, Lewy bodies, prions, apoptosis, caspases, inflammation, excitotoxicity, excitotoxins, excessive nitric oxide production, oxidative stress, proteases, protease inhibitors, neurotrophic factors, cytokines, calcium-dependent processes, signal transduction, altered ionic homeostasis, altered calcium homeostasis, synaptic molecules, adhesion molecules, molecules involved in membrane turnover, cholesterol and lipid metabolism and transport, cytoskeletal molecules, neuronal proteins, brain proteins, and cell necrosis.

113. The method of claim 49, wherein the gene is located on chromosome 10q23, 10q24 or 10q25.

59. A method for identifying a polymorphism associated with Alzheimer'"'"'s disease, comprising:

analyzing a polymorphism on chromosome 10q for association with Alzheimer'"'"'s disease.

63. The method of claim 59, wherein the polymorphism is located about 5 cM around and including D10S583, or about 4 cM around and including D10S583, or about 3 cM around and including D10S583, or about 2 cM around D10S583, or about 1 cM around and including D10S583, or about 0.5 cM around and including D1S583, or about 0.25 cM around and including D10S583, or about 0.1 cM around and including D10S583.

64. The method of claim 59, wherein the polymorphism is located about 30 Mb around and including D10S583, or about 28 Mb around and including D10S583, or about 20 Mb around and including D10S583, or about 15 Mb around and including D10S583, or about 10 Mb around and including D10S583.

65. The method of claim 59, wherein the polymorphism is located about 5 Mb around and including D10S583, or about 2.5 Mb around and including D10S583, or about 1 Mb around and including D10S583 or about 500 kb around and including D10S583, or about 200 kb around and including D10S583, or about 100 kb around and including D10S583, or about 50 kb around and including D10S583, or about 40 kb around and including D10S583, or about 20 kb around and including D10S583, or about 10 kb around and including D10S583, or about 5 kb around and including D10S583, or about 1 kb around and including D10S583.

66. The method of claim 59, wherein the polymorphism is located in a region of chromosome 10 selected from the group consisting of:

(a) the region extending about 50 cM, or about 45 cM, or about 33 cM, or about 30 cM, or about 25 cM, or about 21 cM, or about 15 cM, or about 10 cM, or about 5 cM, or about 4 cM, or about 3 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 60 cM, or about 55 cM, or about 50 cM, or about 45 cM, or about 40 cM, or about 35 cM, or about 30 cM, or about 25 cM, or about 20 cM, or about 15 cM, or about 13 cM, or about 12 cM, or about 9 cM, or about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending from and including marker D10S583 to the terminus of the q arm of chromosome 10,

(d) the region extending from and including marker D10S583 to the centromere of chromosome 10,

(e) the region extending about 62 Mb, about 55 Mb, or about 50 Mb, or about 32 Mb, or about 28 Mb, or about 25 Mb, or about 20 Mb, or about 15 Mb, or about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb proximal from and including marker D10S583,

(f) the region extending about 45 Mb, or about 40 Mb, or about 35 Mb, or about 30 Mb, or about 25 Mb, or about 20 Mb, or about 16 Mb, or about 14 Mb, or about 13 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb distal from and including marker D10S583,

(g) the region between D10S564 and D10S583, inclusive,

(h) the region between D10S583 and D10S1710, inclusive,

(i) the region between D10S583 and D10S566, inclusive,

(j) the region between D10S583 and D10S1671, inclusive and

(k) the region between D10S583 and D10S1741, inclusive.

67. The method of claim 59, wherein the polymorphism is located in a region of chromosome 10 selected from the group consisting of:

(a) the region extending about 5 cM, or about 4 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 80 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb proximal from and including marker D10S583; and

(d) the region extending about 10 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb distal from and including marker D10S583.

68. The method of claim 59, wherein the association between the polymorphism and Alzheimer'"'"'s disease yields a positive result in a family-based test for association.

69. The method of claim 68 wherein the positive result is a P value less than or equal to 0.05.

70. The method of claim 68, wherein the positive result is a P value less than 0.05.

60. A method for identifying a polymorphism associated with Alzheimer'"'"'s disease, comprising analyzing a polymorphism on chromosome 10 for association with Alzheimer'"'"'s disease, wherein the polymorphism is located in the region of 10q22, 10q23, 10q24, 10q25 or 10q26.

190. The method of claim 60, wherein the polymorphism is located on chromosome 10q23, 10q24 or 10q25.

227. The method of claim 60, wherein the polymorphism is located within the PLAU gene.

228. The method of claim 60, wherein the polymorphism is located within the TLL2 gene.

229. The method of claim 60, wherein the polymorphism is located within the PSAP gene.

230. The method of claim 60, wherein the polymorphism is located within the PSD gene.

231. The method of claim 60, wherein the polymorphism is located within the KIAA0904 gene.

232. The method of claim 60, wherein the polymorphism is located within the NFKB2 gene.

233. The method of claim 60, wherein the polymorphism is located within the PPP3CB gene.

234. The method of claim 60, wherein the polymorphism is located within the CH25H gene.

235. The method of claim 60, wherein the polymorphism is located within the FERIL3 gene.

61. A method for identifying a polymorphism associated with Alzheimer'"'"'s disease, comprising analyzing a polymorphism on chromosome 10 for association with Alzheimer'"'"'s disease, wherein the polymorphism is located in the region of 10q22, 10q23 or 10q24.

191. The method of claim 61, wherein the polymorphism is located on chromosome 10q23, 10q24 or 10q25.

236. The method of claim 61, wherein the polymorphism is located within the PLAU gene.

237. The method of claim 61, wherein the polymorphism is located within the TLL2 gene.

238. The method of claim 61, wherein the polymorphism is located within the PSAP gene.

239. The method of claim 61, wherein the polymorphism is located within the PSD gene.

240. The method of claim 61, wherein the polymorphism is located within the KIAA0904 gene.

241. The method of claim 61, wherein the polymorphism is located within the NFKB2 gene.

242. The method of claim 61, wherein the polymorphism is located within the PPP3CB gene.

243. The method of claim 61, wherein the polymorphism is located within the CH25H gene.

244. The method of claim 61, wherein the polymorphism is located within the FERIL3 gene.

62. A method for identifying a polymorphism associated with Alzheimer'"'"'s disease comprising, analyzing a polymorphism on chromosome 10 for association with Alzheimer'"'"'s disease, wherein the polymorphism is located is located about 30 cM around and including D10S583, or about 20 cM around and including D10S583, or about 15 cM around and including D10S583, or about 12 cM around and including D10S583, or about 10 cM around and including D10S583.

71. A combination, comprising:

two or more oligonucleotides that hybridize to, adjacent to, or to DNA flanking a DNA segment on chromosome 10;

wherein

the DNA segment comprises a polymorphism that is associated with AD,

at least two of the oligonucleotides hybridize to, adjacent to, or to DNA flanking different DNA segments.

72. The combination of claim 71, wherein the DNA segment is on chromosome 10q.

73. The combination of claim 71, wherein the DNA segment is on chromosome 10q22, 10q23, 10q24, 10q25 or 10q26.

74. The combination of claim 71, wherein the DNA segment is on chromosome 10q22, 10q23 or 10q24.

75. The combination of claim 71, wherein the DNA segment is located in a region of chromosome 10 about 30 cM around and including D10S583, or about 20 cM around and including D10S583, or about 15 cM around and including D10S583, or about 12 cM around and including D10S583, or about 10 cM around and including D10S583.

76. The combination of claim 71, wherein the DNA segment is located in a region of chromosome 10 about 5 cM around and including D10S583, or about 4cM around and including D10S583, or about 3 cM around and including D10S583, or about 2 cM around D10S583, or about 1 cM around and including D10S583, or about 0.5 cM around and including D10S583, or about 0.25 cM around and including D10S583, or about 0.1 cM around and including D10S583.

77. The combination of claim 71, wherein the DNA segment is located in a region of chromosome 10 about 30 Mb around and including D10S583, or about 28 Mb around and including D10S583, or about 20 Mb around and including D10S583, or about 15 Mb around and including D10S583, or about 10 Mb around and including D10S583.

78. The combination of claim 71, wherein the DNA segment is located in a region of chromosome 10 about 5 Mb around and including D10S583, or about 2.5 Mb around and including D10S583, or about 1 Mb around and including D10S583 or about 500 kb around and including D10S583, or about 200 kb around and including D10S583, or about 100 kb around and including D10S583, or about 50 kb around and including D10S583, or about 40 kb around and including D10S583, or about 20 kb around and including D10S583, or about 10 kb around and including D10S583, or about 5 kb around and including D10S583, or about 1 kb around and including D10S583.

79. The combination of claim 71, wherein the DNA segment is located in one or more of the following regions of chromosome 10:

(a) the region extending about 50 cM, or about 45 cM, or about 33 cM, or about 30 cM, or about 25 cM, or about 21 cM, or about 15 cM, or about 10 cM, or about 5 cM, or about 4 cM, or about 3 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 60 cM, or about 55 cM, or about 50 cM, or about 45 cM, or about 40 cM, or about 35 cM, or about 30 cM, or about 25 cM, or about 20 cM, or about 15 cM, or about 13 cM, or about 12 cM, or about 9 cM, or about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending from and including marker D10S583 to the terminus of the q arm of chromosome 10,

(d) the region extending from and including marker D10S583 to the centromere of chromosome 10,

(e) the region extending about 62 Mb, about 55 Mb, or about 50 Mb, or about 32 Mb, or about 28 Mb, or about 25 Mb, or about 20 Mb, or about 15 Mb, or about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb proximal from and including marker D10S583,

(f) the region extending about 45 Mb, or about 40 Mb, or about 35 Mb, or about 30 Mb, or about 25 Mb, or about 20 Mb, or about 16 Mb, or about 14 Mb, or about 13 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb distal from and including marker D10S583,

(g) the region between D10S564 and D10S583, inclusive,

(h) the region between D10S583 and D10S1710, inclusive,

(i) the region between D10S583 and D10S566, inclusive,

(j) the region between D10S583 and D10S1671, inclusive and

(k) the region between D10S583 and D10S1741, inclusive.

80. The combination of claim 71, wherein the DNA segment is located in one or more of the following regions of chromosome 10:

(a) the region extending about 5 cM, or about 4 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 80 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb proximal from and including marker D10S583; and

(d) the region extending about 10 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb distal from and including marker D10S583.

81. The combination of claim 71, wherein the polymorphism is D10S583.

82. A kit, comprising:

two or more oligonucleotides that hybridize to, adjacent to, or to DNA flanking a DNA segment on chromosome 10; and

instructions describing procedures for using the oligonucleotide(s) in the detection of one or more polymorphisms on chromosome 10 associated with AD, wherein

the DNA segment comprises a polymorphic site at which a polymorphism that is associated with AD occurs,

at least two of the oligonucleotides hybridize to, adjacent to, or to DNA flanking different DNA segments.

87. The kit of claim 82, wherein the polymorphism or polymorphisms are located on chromosome 10q.

88. The kit of claim 82, wherein the polymorphism or polymorphisms are located on chromosome 10q22, 10q23, 10q24, 10q25 and/or 10q26.

89. The kit of claim 82, wherein the polymorphism or polymorphisms are located on chromosome 10q22, 10q23 and/or 10q24.

90. The kit of claim 82, wherein the polymorphism or polymorphisms are located in a region of chromosome 10 about 30 cM around and including D10S583, or about 20 cM around and including D10S583, or about 15 cM around and including D10S583, or about 12 cM around and including D10S583, or about 10 cM around and including D10S583.

91. The kit of claim 82, wherein the polymorphism or polymorphisms are located in a region of chromosome 10 about 5 cM around and including D10S583, or about 4 cM around and including D10S583, or about 3 cM around and including D10S583, or about 2 cM around D10S583, or about 1 cM around and including D10S583, or about 0.5 cM around and including D10S583, or about 0.25 cM around and including D10S583, or about 0.1 cM around and including D10S583.

92. The kit of claim 82, wherein the polymorphism or polymorphisms are located in a region of chromosome 10 about 30 Mb around and including D10S583, or about 28 Mb around and including D10S583, or about 20 Mb around and including D10S583, or about 15 Mb around and including D10S583, or about 10 Mb around and including D10S583.

93. The kit of claim 82, wherein the polymorphism or polymorphisms are located in a region of chromosome 10 about 5 Mb around and including D10S583, or about 2.5 Mb around and including D10S583, or about 1 Mb around and including D10S583 or about 500 kb around and including D10S583, or about 200 kb around and including D10S583, or about 100 kb around and including D10S583, or about 50 kb around and including D10S583, or about 40 kb around and including D10S583, or about 20 kb around and including D10S583, or about 10 kb around and including D10S583, or about 5 kb around and including D10S583, or about 1 kb around and including D10S583.

94. The kit of claim 82, wherein the polymorphism or polymorphisms are located one or more of the following regions of chromosome 10:

(a) the region extending about 50 cM, or about 45 cM, or about 33 cM, or about 30 cM, or about 25 cM, or about 21 cM, or about 15 cM, or about 10 cM, or about 5 cM, or about 4 cM, or about 3 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 60 cM, or about 55 cM, or about 50 cM, or about 45 cM, or about 40 cM, or about 35 cM, or about 30 cM, or about 25 cM, or about 20 cM, or about 15 cM, or about 13 cM, or about 12 cM, or about 9 cM, or about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending from and including marker D10S583 to the terminus of the q arm of chromosome 10,

(d) the region extending from and including marker D10S583 to the centromere of chromosome 10,

(e) the region extending about 62 Mb, about 55 Mb, or about 50 Mb, or about 32 Mb, or about 28 Mb, or about 25 Mb, or about 20 Mb, or about 15 Mb, or about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb proximal from and including marker D10S583,

(f) the region extending about 45 Mb, or about 40 Mb, or about 35 Mb, or about 30 Mb, or about 25 Mb, or about 20 Mb, or about 16 Mb, or about 14 Mb, or about 13 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb distal from and including marker D10S583,

(g) the region between D10S564 and D10S583, inclusive,

(h) the region between D10S583 and D10S1710, inclusive,

(i) the region between D10S583 and D10S566, inclusive,

(j) the region between D10S583 and D10S1671, inclusive and

(k) the region between D10S583 and D10S1741, inclusive.

95. The kit of claim 82, wherein the polymorphism or polymorphisms are located one or more of the following regions of chromosome 10:

(a) the region extending about 5 cM, or about 4 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 80 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb proximal from and including marker D10S583; and

(d) the region extending about 10 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb distal from and including marker D10S583.

96. The kit of claim 82, wherein the instructions describe procedures for using the oligonucleotide(s) in methods of detecting the presence or absence of two or more polymorphisms associated with AD.

83. A kit, comprising:

two or more oligonucleotides that hybridize to, adjacent to, or to DNA flanking a DNA segment on chromosome 10; and

instructions describing procedures for using the oligonucleotide(s) in methods of detecting the presence or absence of one or more polymorphisms on chormosome 10 associated with AD, wherein

the DNA segment comprises a polymorphic site at which a polymorphism that is associated with AD occurs,

at least two of the oligonucleotides hybridize to, adjacent to, or to DNA flanking different DNA segments, and

the procedures provide results on which to base a determination of a predisposition to or occurrence of AD in a subject.

84. A kit, comprising:

two or more oligonucleotides that hybridize to, adjacent to, or to DNA flanking a DNA segment on chromosome 10; and

instructions describing procedures for using the oligonucleotide(s) in methods of detecting the presence or absence of one or more polymorphisms on chormosome 10 associated with AD, wherein

the DNA segment comprises a polymorphic site at which a polymorphism that is associated with AD occurs,

at least two of the oligonucleotides hybridize to, adjacent to, or to DNA flanking different DNA segments, and the procedures provide results on which to base a prediction of a subject'"'"'s response to a treatment for AD.

85. A kit, comprising:

two or more oligonucleotides that hybridize to, adjacent to, or to DNA flanking a DNA segment on chromosome 10; and

instructions describing procedures for using the oligonucleotide(s) in methods of detecting the presence or absence of one or more polymorphisms on chromosome 10 associated with AD,

the DNA segment comprises a polymorphic site at which a polymorphism that is associated with AD occurs,

at least two of the oligonucleotides hybridize to, adjacent to, or to DNA flanking different DNA segments, and

the procedures provide results on which to base a treatment of AD in a subject.

86. A kit, comprising:

one or more oligonucleotides that hybridize to, adjacent to, or to DNA flanking a DNA segment on chromosome 10; and

one or more control samples, wherein

the DNA segment comprises a polymorphic site at which a polymorphism that is associated with AD occurs, and

the one or more control samples comprise the DNA segment in which the polymorphic site does not contain a polymorphism associated with AD and/or the DNA segment in which the polymorphic site does contain a polymorphism associated with AD.

102. A combination comprising:

two or more genetic markers on chromosome 10 that are associated with Alzheimer'"'"'s disease either individually or as a combination.

103. The combination of claim 102, wherein the genetic markers are located on chromosome 10q.

104. The combination of claim 102, wherein each of the genetic markers is located on chromosome 10q22, 10q23, 10q24, 10q25 or 10q26.

105. The combination of claim 102, wherein each of the genetic markers is located on chromosome 10q22, 10q23 or 10q24.

106. The combination of claim 102, wherein each of the genetic markers is located in a region of chromosome 10 about 30 cM around and including D10S583, or about 20 cM around and including D10S583, or about 15 cM around and including D10S583, or about 12 cM around and including D10S583, or about 10 cM around and including D10S583.

107. The combination of claim 102, wherein each of the genetic markers is located in a region of chromosome 10 about 5 cM around and including D10S583, or about 4 cM around and including D10S583, or about 3 cM around and including D10S583, or about 2 cM around D10S583, or about 1 cM around and including D10S583, or about 0.5 cM around and including D10S583, or about 0.25 cM around and including D10S583, or about 0.1 cM around and including D10S583.

108. The combination of claim 102, wherein each of the genetic markers is located in a region of chromosome 10 about 30 Mb around and including D10S583, or about 28 Mb around and including D10S583, or about 20 Mb around and including D10S583, or about 15 Mb around and including D10S583, or about 10 Mb around and including D10S583.

109. The combination of claim 102, wherein each of the genetic markers is located in a region of chromosome 10 about 5 Mb around and including D10S583, or about 2.5 Mb around and including D10S583, or about 1 Mb around and including D10S583 or about 500 kb around and including D10S583, or about 200 kb around and including D10S583, or about 100 kb around and including D10S583, or about 50 kb around and including D10S583, or about 40 kb around and including D10S583, or about 20 kb around and including D10S583, or about 10 kb around and including D10S583, or about 5 kb around and including D10S583, or about 1 kb around and including D10S583.

110. The combination of claim 102, wherein each of the genetic markers is located one or more of the following regions of chromosome 10:

(a) the region extending about 50 cM, or about 45 cM, or about 33 cM, or about 30 cM, or about 25 cM, or about 21 cM, or about 15 cM, or about 10 cM, or about 5 cM, or about 4 cM, or about 3 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 60 cM, or about 55 cM, or about 50 cM, or about 45 cM, or about 40 cM, or about 35 cM, or about 30 cM, or about 25 cM, or about 20 cM, or about 15 cM, or about 13 cM, or about 12 cM, or about 9 cM, or about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending from and including marker D10S583 to the terminus of the q arm of chromosome 10,

(d) the region extending from and including marker D10S583 to the centromere of chromosome 10,

(e) the region extending about 62 Mb, about 55 Mb, or about 50 Mb, or about 32 Mb, or about 28 Mb, or about 25 Mb, or about 20 Mb, or about 15 Mb, or about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb proximal from and including marker D10S583,

(f) the region extending about 45 Mb, or about 40 Mb, or about 35 Mb, or about 30 Mb, or about 25 Mb, or about 20 Mb, or about 16 Mb, or about 14 Mb, or about 13 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb distal from and including marker D10S583,

(g) the region between D10S564 and D10S583, inclusive,

(h) the region between D10S583 and D10S1710, inclusive,

(i) the region between D10S583 and D10S566, inclusive,

(j) the region between D10S583 and D10S1671, inclusive and

(k) the region between D10S583 and D10S1741, inclusive.

111. The combination of claim 102, wherein each of the genetic markers is located one or more of the following regions of chromosome 10:

(a) the region extending about 5 cM, or about 4 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 80 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb proximal from and including marker D10S583; and

(d) the region extending about 10 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb distal from and including marker D10S583.

124. A method for detecting the presence or absence in a subject of polymorphisms associated with Alzheimer'"'"'s disease, comprising analyzing chromosome 10 of the subject for two or more polymorphisms associated with Alzheimer'"'"'s disease, wherein at least two of the polymorphisms are associated with different AD DNA segments.

125. The method of claim 124, wherein the two or more polymorphisms are located on chromosome 10q.

126. The method of claim 124, wherein each of the two or more polymorphisms is located on chromosome 10q22, 10q23, 10q24, 10q25 or 10q26.

127. The method of claim 124, wherein each of the two or more polymorphisms is located on chromosome 10q22, 10q23 or 10q24.

128. The method of claim 124, wherein each of the two or more polymorphisms is located on chromosome 10q23, 10q24 or 10q25.

129. The method of claim 124, wherein each of the two or more polymorphisms is located in a region of chromosome 10 about 30 cM around and including D10S583, or about 20 cM around and including D10S583, or about 15 cM around and including D10S583, or about 12 cM around and including D10S583, or about 10 cM around and including D10S583.

130. The method of claim 124, wherein each of the two or more polymorphisms is located in a region of chromosome 10 about 5 cM around and including D10S583, or about 4 cM around and including D10S583, or about 3 cM around and including D10S583, or about 2 cM around D10S583, or about 1 cM around and including D10S583, or about 0.5 cM around and including D10S583, or about 0.25 cM around and including D10S583, or about 0.1 cM around and including D10S583.

131. The method of claim 124, wherein each of the two or more polymorphisms is located in a region of chromosome 10 about 30 Mb around and including D10S583, or about 28 Mb around and including D10S583, or about 20 Mb around and including D10S583, or about 15 Mb around and including D10S583, or about 10 Mb around and including D10S583.

132. The method of claim 124, wherein each of the two or more polymorphisms is located in a region of chromosome 10 about 5 Mb around and including D10S583, or about 2.5 Mb around and including D10S583, or about 1 Mb around and including D10S583 or about 500 kb around and including D10S583, or about 200 kb around and including D10S583, or about 100 kb around and including D10S583, or about 50 kb around and including D10S583, or about 40 kb around and including D10S583, or about 20 kb around and including D10S583, or about 10 kb around and including D10S583, or about 5 kb around and including D10S583, or about 1 kb around and including D10S583.

133. The method of claim 124, wherein each of the two or more polymorphisms is located one or more of the following regions of chromosome 10:

(a) the region extending about 50 cM, or about 45 cM, or about 33 cM, or about 30 cM, or about 25 cM, or about 21 cM, or about 15 cM, or about 10 cM, or about 5 cM, or about 4 cM, or about 3 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 60 cM, or about 55 cM, or about 50 cM, or about 45 cM, or about 40 cM, or about 35 cM, or about 30 cM, or about 25 cM, or about 20 cM, or about 15 cM, or about 13 cM, or about 12 cM, or about 9 cM, or about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending from and including marker D10S583 to the terminus of the q arm of chromosome 10,

(d) the region extending from and including marker D10S583 to the centromere of chromosome 10,

(e) the region extending about 62 Mb, about 55 Mb, or about 50 Mb, or about 32 Mb, or about 28 Mb, or about 25 Mb, or about 20 Mb, or about 15 Mb, or about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb proximal from and including marker D10S583,

(f) the region extending about 45 Mb, or about 40 Mb, or about 35 Mb, or about 30 Mb, or about 25 Mb, or about 20 Mb, or about 16 Mb, or about 14 Mb, or about 13 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb distal from and including marker D10S583,

(g) the region between D10S564 and D10S583, inclusive,

(h) the region between D10S583 and D10S1710, inclusive,

(i) the region between D10S583 and D10S566, inclusive,

(j) the region between D10S583 and D10S1671, inclusive and

(k) the region between D10S583 and D10S1741, inclusive.

134. The method of claim 124, wherein each of the two or more polymorphisms is located one or more of the following regions of chromosome 10:

(a) the region extending about 5 cM, or about 4 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 80 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb proximal from and including marker D10S583; and

(d) the region extending about 10 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb distal from and including marker D10S583.

135. A method of determining the level of risk for Alzheimer'"'"'s disease in a subject, comprising:

analyzing chromosome 10 of the subject for the presence or absence of one or more polymorphisms associated with Alzheimer'"'"'s disease, wherein the one or more polymorphisms are indicative of an increased or decreased risk for Alzheimer'"'"'s disease.

136. The method of claim 135, wherein the association between the polymorphism and Alzheimer'"'"'s disease yields a positive result in a family-based test for association.

137. The method of claim 136, wherein the positive result is a P value less than or equal to 0.05.

138. The method of claim 136, wherein the positive result is a P value less than 0.05.

139. The method of claim 135, wherein the association between the polymorphism and Alzheimer'"'"'s disease yields a result in a family-based test for association that is indicative of linkage disequilibrium between the polymorphism and an allele associated with Alzheimer'"'"'s disease.

140. The method of claim 135, wherein the polymorphism is associated with unaffected members of a family having members affected with Alzheimer'"'"'s disease and is indicative of a decreased risk for Alzheimer'"'"'s disease.

141. The method of claim 140, wherein the association between the polymorphism and unaffected members of a family having members affected with Alzheimer'"'"'s disease yields a positive result in a family-based test for association.

142. The method of claim 141, wherein the positive result is a P value less than or equal to 0.05.

143. The method of claim 141, wherein the positive result is a P value less than 0.05.

144. The method of claim 135, wherein the polymorphism is under-represented in cases of a case-control study.

145. The method of claim 135, wherein the polymorphism is an allele of D10S583 and the presence of the allele of D10S583 is indicative of a decreased risk for AD.

146. The method of claim 145, wherein the allele of D10S583 is about 210 bp.

147. The method of claim 145, wherein the allele of D10S583 is 209 bp.

148. The method of claim 145, wherein the allele of D10S583 is 211 bp.

149. The method of claim 135, wherein the polymorphism is associated with affected members of a family having members affected with Alzheimer'"'"'s disease and is indicative of an increased risk for Alzheimer'"'"'s disease.

150. The method of claim 149, wherein the association between the polymorphism and affected members of a family having members affected with Alzheimer'"'"'s disease yields a positive result in a family-based test for association.

151. The method of claim 150, wherein the positive result is a P value less than or equal to 0.05.

152. The method of claim 150, wherein the positive result is a P value less than 0.05.

153. The method of claim 135, wherein the polymorphism is over-represented in cases of a case-control study.

154. The method of claim 135, wherein the one or more polymorphisms are located on chromosome 10q.

155. The method of claim 135, wherein each of the one or more polymorphisms is located on chromosome 10q22, 10q23, 10q24, 10q25 or 10q26.

156. The method of claim 135, wherein each of the one or more polymorphisms is located on chromosome 10q22, 10q23 or 10q24.

157. The method of claim 135, wherein each of the one or more polymorphisms is located on chromosome 10q23, 10q24 or 10q25.

158. The method of claim 135, wherein each of the one or more polymorphisms is located in a region of chromosome 10 about 30 cM around and including D10S583, or about 20 cM around and including D10S583, or about 15 cM around and including D10S583, or about 12 cM around and including D10S583, or about 10 cM around and including D10S583.

159. The method of claim 135, wherein each of the one or more polymorphisms are located in a region of chromosome 10 about 5 cM around and including D10S583, or about 4 cM around and including D10S583, or about 3 cM around and including D10S583, or about 2 cM around D10S583, or about 1 cM around and including D10S583, or about 0.5 cM around and including D10S583, or about 0.25 cM around and including D10S583, or about 0.1 cM around and including D10S583.

160. The method of claim 135, wherein each of the one or more polymorphisms is located in a region of chromosome 10 about 30 Mb around and including D10S583, or about 28 Mb around and including D10S583, or about 20 Mb around and including D10S583, or about 15 Mb around and including D10S583, or about 10 Mb around and including D10S583.

161. The method of claim 135, wherein each of the one or more polymorphisms is located in a region of chromosome 10 about 5 Mb around and including D10S583, or about 2.5 Mb around and including D10S583, or about 1 Mb around and including D10S583 or about 500 kb around and including D10S583, or about 200 kb around and including D10S583, or about 100 kb around and including D10S583, or about 50 kb around and including D10S583, or about 40 kb around and including D10S583, or about 20 kb around and including D10S583, or about 10 kb around and including D10S583, or about 5 kb around and including D10S583, or about 1 kb around and including D10S583.

162. The method of claim 135, wherein each of the one or more polymorphisms is located in one or more of the following regions of chromosome 10:

(a) the region extending about 50 cM, or about 45 cM, or about 33 cM, or about 30 cM, or about 25 cM, or about 21 cM, or about 15 cM, or about 10 cM, or about 5 cM, or about 4 cM, or about 3 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 60 cM, or about 55 cM, or about 50 cM, or about 45 cM, or about 40 cM, or about 35 cM, or about 30 cM, or about 25 cM, or about 20 cM, or about 15 cM, or about 13 cM, or about 12 cM, or about 9 cM, or about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending from and including marker D10S583 to the terminus of the q arm of chromosome 10,

(d) the region extending from and including marker D10S583 to the centromere of chromosome 10,

(e) the region extending about 62 Mb, about 55 Mb, or about 50 Mb, or about 32 Mb, or about 28 Mb, or about 25 Mb, or about 20 Mb, or about 15 Mb, or about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb proximal from and including marker D10S583,

(f) the region extending about 45 Mb, or about 40 Mb, or about 35 Mb, or about 30 Mb, or about 25 Mb, or about 20 Mb, or about 16 Mb, or about 14 Mb, or about 13 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb distal from and including marker D10S583,

(g) the region between D10S564 and D10S583, inclusive,

(h) the region between D10S583 and D10S1710, inclusive,

(i) the region between D10S583 and D10S566, inclusive,

(j) the region between D10S583 and D10S1671, inclusive and

(k) the region between D10S583 and D10S1741, inclusive.

163. The method of claim 135, wherein each of the one or more polymorphisms is located one or more of the following regions of chromosome 10:

(a) the region extending about 5 cM, or about 4 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 80 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb proximal from and including marker D10S583; and

(d) the region extending about 10 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb distal from and including marker D10S583.

164. A method for detecting the presence or absence in a subject of a combination of polymorphisms associated with Alzheimer'"'"'s disease, comprising analyzing chromosome 10 of the subject for a combination of polymorphisms associated with Alzheimer'"'"'s disease.

165. The method of claim 164, wherein the polymorphisms are located on chromosome 10q.

166. The method of claim 164, wherein each of the polymorphisms is located on chromosome 10q22, 10q23, 10q24, 10q25 or 10q26.

167. The method of claim 164, wherein each of the polymorphisms is located on chromosome 10q22, 10q23 or 10q24.

168. The method of claim 164, wherein each of the polymorphisms is located on chromosome 10q23, 10q24 or 10q25.

169. The method of claim 164, wherein each of the polymorphisms is located about 30 cM around and including D10S583, or about 20 cM around and including D10S583, or about 15 cM around and including D10S583, or about 12 cM around and including D10S583, or about 10 cM around and including D10S583.

170. The method of claim 164, wherein each of the polymorphisms is located about 5 cM around and including D10S583, or about 4 cM around and including D10S583, or about 3 cM around and including D10S583, or about 2 cM around D10S583, or about 1 cM around and including D10S583, or about 0.5 cM around and including D10S583, or about 0.25 cM around and including D10S583, or about 0.1 cM around and including D10S583.

171. The method of claim 164, wherein each of the polymorphisms is located about 30 Mb around and including D10S583, or about 28 Mb around and including D10S583, or about 20 Mb around and including D10S583, or about 15 Mb around and including D10S583, or about 10 Mb around and including D10S583.

172. The method of claim 164, wherein each of the polymorphisms is located about 5 Mb around and including D10S583, or about 2.5 Mb around and including D10S583, or about 1 Mb around and including D10S583 or about 500 kb around and including D10S583, or about 200 kb around and including D10S583, or about 100 kb around and including D10S583, or about 50 kb around and including D10S583, or about 40 kb around and including D10S583, or about 20 kb around and including D10S583, or about 10 kb around and including D10S583, or about 5 kb around and including D10S583, or about 1 kb around and including D10S583.

173. The method of claim 164, wherein each of the polymorphisms is located in one or more of the following regions of chromosome 10:

(a) the region extending about 50 cM, or about 45 cM, or about 33 cM, or about 30 cM, or about 25 cM, or about 21 cM, or about 15 cM, or about 10 cM, or about 5 cM, or about 4 cM, or about 3 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 60 cM, or about 55 cM, or about 50 cM, or about-45 cM, or about 40 cM, or about 35 cM, or about 30 cM, or about 25 cM, or about 20 cM, or about 15 cM, or about 13 cM, or about 12 cM, or about 9 cM, or about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending from and including marker D10S583 to the terminus of the q arm of chromosome 10,

(d) the region extending from and including marker D10S583 to the centromere of chromosome 10,

(e) the region extending about 62 Mb, about 55 Mb, or about 50 Mb, or about 32 Mb, or about 28 Mb, or about 25 Mb, or about 20 Mb, or about 15 Mb, or about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.3 Mb, or about 0.2 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb proximal from and including marker D10S583,

(f) the region extending about 45 Mb, or about 40 Mb, or about 35 Mb, or about 30 Mb, or about 25 Mb, or about 20 Mb, or about 16 Mb, or about 14 Mb, or about 13 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 0.5 Mb, or about 0.1 Mb, or about 0.05 Mb, or about 0.01 Mb, or about 1 kb distal from and including marker D10S583,

(g) the region between D10S564 and D10S583, inclusive,

(h) the region between D10S583 and D10S1710, inclusive,

(i) the region between D10S583 and D10S566, inclusive,

(j) the region between D10S583 and D10S1671, inclusive and

(k) the region between D10S583 and D10S1741, inclusive.

174. The method of claim 164, wherein each of the polymorphisms is located in one or more of the following regions of chromosome 10:

(a) the region extending about 5 cM, or about 4 cM, or about 2.7 cM, or about 2.5 cM, or about 2 cM, or about 1.5 cM, or about 1 cM, or about 0.5 cM, or about 0.1 cM proximal (centromeric) from and including marker D10S583,

(b) the region extending about 5 cM, or about 2.5 cM, or about 1 cM, or about 0.5 cM or about 0.1 cM distal (telomeric) from and including marker D10S583,

(c) the region extending about 10 Mb, or about 5 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 80 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb proximal from and including marker D10S583; and

(d) the region extending about 10 Mb, or about 8 Mb, or about 5 Mb, or about 4 Mb, or about 3 Mb, or about 2 Mb, or about 1 Mb, or about 500 kb, or about 300 kb, or about 200 kb, or about 100 kb, or about 50 kb, or about 10 kb, or about 5 kb, or about 1 kb distal from and including marker D10S583.