Method and System to Detect, Diagnose, and Monitor the Progression of Alzheimer's Disease

• US 20110086925A1
• Filed: 06/09/2010
• Published: 04/14/2011
• Est. Priority Date: 06/09/2009
• Status: Abandoned Application

• Current Assignee: Banner Research Institute
• Original Assignee: Banner Research Institute
• Inventors: Coleman, Paul D., Mastroeni, Diego, Grover, Andrew, Rogers, Joseph
• Application Number:
  US12/797,591
• Publication Number:
  US 20110086925A1
• Time in Patent Office: Days
• US Class Current: 514/789
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 33/5308 for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
• CPC Class Codes: G01N 33/56972 White blood cells
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

Various embodiments provide methods for the detection, the diagnosis, and/or the progression monitoring of Alzheimer'"'"'s disease by observing the epigenetic markers in leukocytes. Methods for determining a state of Alzheimer'"'"'s disease are provided. Accordingly, these methods can comprise the steps of placing a sample comprising at least one blood component onto a substrate labeling the sample to identify at least one epigenetic marker; determining an amount of the at least one epigenetic marker; comparing the amount to a reference value; and determining a state of Alzheimer'"'"'s disease.

Claims

1. A method for determining a state of Alzheimer'"'"'s disease, the method comprising:

placing a sample comprising at least one blood component onto a substrate;

labeling the sample to identify at least one epigenetic marker;

determining an amount of the at least one epigenetic marker;

comparing the amount to a reference value; and

determining a state of Alzheimer'"'"'s disease.

2. The method according to claim 1, further comprising separating blood into the at least blood component and other blood components, to produce the sample comprising at least one blood component onto a substrate.

3. The method according to claim 1, wherein the determining an amount of the at least one epigenetic marker comprising measure an intensity of the label.

4. The method according to claim 1, further comprising binding an antibody to the at least one epigenetic marker.

5. The method according to claim 1, further comprising preparing a treatment plan for a patient supplying the sample.

6. The method according to claim 5, further comprising treating the patient with a therapeutic substance.

7. The method according to claim 6, further comprising:

placing a second sample comprising the at least one blood component onto the substrate;

labeling the second sample to identify the at least one epigenetic marker;

determining a second amount of the at least one epigenetic marker;

comparing the second amount to the reference value; and

determining a dosage of the therapeutic substance.

8. The method according to claim 6, further comprising evaluating the efficacy of the therapeutic substance.

9. The method according to claim 8, wherein the evaluating the efficacy of the therapeutic substance further comprises comparing a plurality of epigenetic markers over time.

10. The method according to claim 5, further comprising estimating the likelihood that the patient will develop clinical signs of Alzheimer'"'"'s disease within a specified time.

11. The method according to claim 10, wherein the estimating the likelihood further comprises comparing a plurality of a patent'"'"'s epigenetic marker amounts over time.

12. The method according to claim 5, further comprising estimating the patient'"'"'s likely rate of Alzheimer'"'"'s disease progression.

13. The method according to claim 1, further comprising:

placing a second sample comprising the at least one blood component onto the substrate;

labeling the second sample to identify the at least one epigenetic marker;

determining a second amount of the at least one epigenetic marker;

comparing the second amount to the reference value; and

further determining a state of Alzheimer'"'"'s disease.

14. A method for determining a state of Alzheimer'"'"'s disease in a patient, the method comprising:

receiving a blood sample from a patient;

separating leukocytes from the blood sample;

binding an antibody to at least one epigenetic marker in the leukocytes;

attaching a label to the antibody;

determining an amount of the label; and

determining the state of Alzheimer'"'"'s disease in the patient based on the amount of the label.

15. The method according to claim 14, further comprising

binding second antibody to a second epigenetic marker in a second portion of the leukocytes;

attaching a second label to the second antibody;

determining an amount of the second label; and

determining the state of Alzheimer'"'"'s disease in the patient based on the amount of the label and the amount of the second label.

17. The method according to claim 14, further comprising comparing the amount of the label to a reference.

18. The method according to claim 17, wherein the reference is a calibration curve for the amount of the label compared to the epigenetic marker.

19. The method according to claim 14, wherein the at least one epigenetic marker is at least one of a DNA methylation marker and a histone modification marker.

20. The method according to claim 14, wherein the attaching a label to the antibody comprises conjugating an antibody comprising the label to the antibody.

16. The method according to claim 16, further comprising determining the state of Alzheimer'"'"'s disease based on the amount of the label and based on the amount of the second label.

21. A system for determining a state of Alzheimer'"'"'s disease, the apparatus comprising:

a substrate comprising a top surface and a bottom surface;

at least one detail on the top surface of the substrate;

at least one antibody operative to bind at least one epigenetic marker in a sample comprising leukocyte, the at least one antibody located in the at least one detail; and

a reference value comprising a known amount of the at least one epigenetic marker.

22. The system according to claim 21, further comprising:

a second detail on the top surface of the substrate;

a second operative to bind a second epigenetic marker in the sample comprising leukocyte, the second located in the second detail; and

a second reference sample comprising a known amount of the second epigenetic marker.

23. The system according to claim 21, wherein the reference value is located in a reference detail on the top surface of the substrate and located proximate to the at least one detail.

24. The system according to claim 21, further comprising a label operable to identify the at least one antibody.