Methods and compositions for diagnosis, stratification, and monitoring of alzheimer's disease and other neurological disorders in body fluids
First Claim
Patent Images
1. A method of aiding diagnosis of Alzheimer'"'"'s disease (“
- AD”
), comprising comparing a measured level of at least one AD diagnosis biomarker in a biological fluid sample from an individual to a reference level for the biomarker, wherein the AD diagnosis biomarker is selected from the group consisting of GCSF;
IFN-g;
IGFBP-1;
BMP-6;
BMP-4;
Eotaxin-2;
IGFBP-2;
TARC;
RANTES;
ANG;
PARC;
Acrp30;
AgRP(ART);
TIMP-1;
TIMP-2;
ICAM-1;
TRAIL R3;
uPAR;
IGFBP-4;
LEPTIN(OB);
PDGF-BB;
EGF;
BDNF;
NT-3;
NAP-2;
IL-1ra;
MSP-a;
SCF;
TGF-b3;
TNF-b;
MIP-1d;
IL-3;
FGF-6;
IL-6 R;
sTNF RII;
AXL;
bFGF;
FGF-4;
CNTF;
MCP-1;
MIP-1b;
TPO;
VEGF-B;
IL-8;
FAS;
EGF-R.
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Accused Products
Abstract
The inventors have discovered a collection of proteinaceous biomarkers (“AD biomarkers) which can be measured in peripheral biological fluid samples to aid in the diagnosis of neurodegenerative disorders, particularly Alzheimer'"'"'s disease and mild cognitive impairment (MCI). The invention further provides methods of identifying candidate agents for the treatment of Alzheimer'"'"'s disease by testing prospective agents for activity in modulating AD biomarker levels.
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Citations
56 Claims
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1. A method of aiding diagnosis of Alzheimer'"'"'s disease (“
- AD”
), comprising comparing a measured level of at least one AD diagnosis biomarker in a biological fluid sample from an individual to a reference level for the biomarker, wherein the AD diagnosis biomarker is selected from the group consisting of GCSF;
IFN-g;
IGFBP-1;
BMP-6;
BMP-4;
Eotaxin-2;
IGFBP-2;
TARC;
RANTES;
ANG;
PARC;
Acrp30;
AgRP(ART);
TIMP-1;
TIMP-2;
ICAM-1;
TRAIL R3;
uPAR;
IGFBP-4;
LEPTIN(OB);
PDGF-BB;
EGF;
BDNF;
NT-3;
NAP-2;
IL-1ra;
MSP-a;
SCF;
TGF-b3;
TNF-b;
MIP-1d;
IL-3;
FGF-6;
IL-6 R;
sTNF RII;
AXL;
bFGF;
FGF-4;
CNTF;
MCP-1;
MIP-1b;
TPO;
VEGF-B;
IL-8;
FAS;
EGF-R. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 21, 23, 39, 40, 41, 42, 43, 44, 45, 46, 52, 53, 54)
- AD”
-
16. A method of aiding diagnosis of Alzheimer'"'"'s disease (“
- AD”
), comprising;
comparing a measured level of at least 4 AD diagnosis biomarkers, wherein said biomarkers comprise BDNF, PDGF-BB, leptin and RANTES, in a biological fluid sample from an individual to a reference level for each AD diagnosis biomarker. - View Dependent Claims (17, 18, 19, 20, 22)
- AD”
-
24. A method for monitoring progression of Alzheimer'"'"'s disease (AD) in an AD patient, comprising:
- comparing a measured level of at least one AD diagnosis biomarker in a biological fluid sample from an individual to a reference level for the biomarker, wherein the AD diagnosis biomarker is selected from the group consisting of GCSF;
IFN-g;
IGFBP-1;
BMP-6;
BMP-4;
Eotaxin-2;
IGFBP-2;
TARC;
RANTES;
ANG;
PARC;
Acrp30;
AgRP(ART);
TIMP-1;
TIMP-2;
ICAM-1;
TRAIL R3;
uPAR;
IGFBP-4;
LEPTIN(OB);
PDGF-BB;
EGF;
BDNF;
NT-3;
NAP-2;
IL-1ra;
MSP-a;
SCF;
TGF-b3;
TNF-b;
MIP-1d;
IL-3;
FGF-6;
IL-6 R;
sTNF RII;
AXL;
bFGF;
FGF-4;
CNTF;
MCP-1;
MIP-1b;
TPO;
VEGF-B;
IL-8;
FAS;
EGF-R. - View Dependent Claims (25, 26, 27, 28, 29, 30)
- comparing a measured level of at least one AD diagnosis biomarker in a biological fluid sample from an individual to a reference level for the biomarker, wherein the AD diagnosis biomarker is selected from the group consisting of GCSF;
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31. A method for stratifying Alzheimer'"'"'s disease (AD) in an individual, comprising:
comparing measured values for brain derived neurotrophic factor (BDNF) and BB homodimeric platelet derived growth factor (PDGF-BB) levels in a biological fluid sample from said patient with reference values for BDNF and PDGF-BB. - View Dependent Claims (32, 33, 34)
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35. A method of identifying a candidate agent for treatment of Alzheimer'"'"'s Disease, comprising:
- assaying a prospective candidate agent for activity in modulating an AD biomarker, said AD biomarker selected from the group consisting of GCSF;
IFN-g;
IGFBP-1;
BMP-6;
BMP-4;
Eotaxin-2;
IGFBP-2;
TARC;
RANTES;
ANG;
PARC;
Acrp30;
AgRP(ART);
TIMP-1;
TIMP-2;
ICAM-1;
TRAIL R3;
uPAR;
IGFBP-4;
LEPTIN(OB);
PDGF-BB;
EGF;
BDNF;
NT-3;
NAP-2;
IL-1ra;
MSP-a;
SCF;
TGF-b3;
TNF-b;
MIP-1d;
IL-3;
FGF-6;
IL-6 R;
sTNF RII;
AXL;
bFGF;
FGF-4;
CNTF;
MCP-1;
MIP-1b;
TPO;
VEGF-B;
IL-8;
FAS;
EGF-R. - View Dependent Claims (36, 37, 38)
- assaying a prospective candidate agent for activity in modulating an AD biomarker, said AD biomarker selected from the group consisting of GCSF;
- 47. A surface comprising attached thereto, at least one reagent specific for each AD diagnosis biomarker in a set of AD diagnosis biomarkers, wherein said set of AD diagnosis biomarkers comprises BDNF. PDGF-BB, leptin and RANTES.
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48. A surface comprising attached thereto,
a. at least one reagent specific for each AD diagnosis biomarker in a set of AD diagnosis biomarkers, wherein said set of AD diagnosis biomarkers consists of BDNF, PDGF-BB, leptin and RANTES; - and
b. at least one reagent specific for a biomarker that measures sample characteristics. - View Dependent Claims (50, 51)
- and
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55. A set of reference values for AD diagnosis biomarkers comprising BDNF, PDGF-BB, Leptin and RANTES.
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56. A set of reagents specific for AD diagnosis biomarkers, wherein said biomarkers comprise BDNF, PDGF-BB, Leptin and RANTES.
Specification