Methods and compositions for diagnosis, stratification, and monitoring of alzheimer's disease and other neurological disorders in body fluids

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.

1 - 34 . (canceled) 
     
     
         35 . A method of determining whether an individual is a candidate for the treatment of Alzheimer's disease (“AD”) comprising:
 a) quantifying the amounts of a panel of analyte biomarkers in a sample from a test subject; 
 b) comparing the amounts of the biomarkers present in the sample with one or more control samples; 
 c) diagnosing the test subject as suffering from AD based at least in part on a difference between the amounts of the biomarkers present in the sample and the control, and 
 d) selecting an AD treatment for the test subject 
 wherein the panel of analyte biomarkers comprises at least two of GCSF; IFN-gamma; IGFBP-I; BMP-6; BMP-4; Eotaxin-2; IGFBP-2; TARC; RANTES; ANG; PARC; Acrp30; AgRP(ART); TIMP-I; TIMP-2; ICAM-I; TRAIL R3; uPAR; IGFBP-4; LEPTIN(OB); PDGF-BB; EGF; BDNF; NT-3; NAP-2; IL-1ra; MSP-alpha; SCF; TGF-b3; TNF-b; MIP-Idelta; IL-3; FGF-6; IL-6 R; sTNF RII; AXL; bFGF; FGF-4; CNTF; MCP-I; MIP-Ib; TPO; VEGF-B; IL-8; FAS; and EGF-R. 
 
     
     
         36 . The method of  claim 35  wherein the sample is whole blood, serum, or plasma. 
     
     
         37 . The method of  claim 35  wherein the test subject is a human subject. 
     
     
         38 . The method of  claim 35  wherein the panel of analyte biomarkers consists of BDNF, PDGF-BB, Leptin, and Rantes. 
     
     
         39 . The method of  claim 35  wherein the panel of analyte biomarkers consists of sTNF RII, MSP-alpha, uPAR, TPO, MIP-1beta, VEGF-beta, FAS, MCP-1, NAP-2, ICAM-I, TRAIL R3, PARC, ANG, IL-3, MIP-Idelta, IFN-gamma, IL-8, and FGF-6. 
     
     
         40 . The method of  claim 35  wherein the panel of analyte biomarkers consists of IFN-gamma, and IL-8. 
     
     
         41 . The method of  claim 35  wherein the panel of analyte biomarkers further comprises at least one of BTC, SDF-1, MCP-2, IFN-gamma, IGFBP-4, IGF-1 SR, IL-8, GM-CSF, and ANG-2. 
     
     
         42 . The method of  claim 35  wherein the panel of anaylte biomarkers further comprises at least one of lymphotacin, and IL-11. 
     
     
         43 . The method of  claim 35  wherein the panel of anaylte biomarkers comprises at least three of GCSF; IFN-gamma; IGFBP-I; BMP-6; BMP-4; Eotaxin-2; IGFBP-2; TARC; RANTES; ANG; PARC; Acrp30; AgRP(ART); TIMP-I; TIMP-2; ICAM-I; TRAIL R3; uPAR; IGFBP-4; LEPTIN(OB); PDGF-BB; EGF; BDNF; NT-3; NAP-2; IL-1ra; MSP-alpha; SCF; TGF-b3; TNF-b; MIP-1delta; IL-3; FGF-6; IL-6 R; sTNF RII; AXL; bFGF; FGF-4; CNTF; MCP-I; MIP-Ib; TPO; VEGF-B; IL-8; FAS; and EGF-R. 
     
     
         44 . The method of  claim 35  wherein the sample is obtained from the subject immediately prior to measuring the levels of said biomarkers. 
     
     
         45 . The method of  claim 35  wherein the control sample is obtained from the same human individual at an earlier point in time. 
     
     
         46 . The method of  claim 35  wherein the control sample is obtained from a human subject without AD. 
     
     
         47 . The method of  claim 35  wherein the control samples are obtained from a group of individuals without AD. 
     
     
         48 . The method of  claim 35  wherein the level of analytes is measured by affinity-based measurement technology. 
     
     
         49 . The method of  claim 35  wherein the level of analytes is measure by ELONA. 
     
     
         50 . The method of  claim 35  wherein the level of analytes is measured by spectroscopy-based measurement technology. 
     
     
         51 . The method of  claim 35  wherein the level of analytes is measured by MALDI-TOF. 
     
     
         52 . The method of  claim 35  wherein the level of analytes is measured by an antibody-based assays. 
     
     
         53 . The method of  claim 35  wherein the level of analytes is measured by a method comprising at least one of radioimmunoassay, immunoflourescent assay, enzyme immunoassay, chemiluminescent assay, ELISA, immune-PCR, and western blot assay. 
     
     
         54 . The method of  claim 35  wherein the method of comparing the measured levels comprises at least one of Significance Analysis of Microarrarys (SAM), Tree Harvesting, CART, MARS, Self Organizing Maps, Frequent Item Set, and Bayesian Networks. 
     
     
         55 . The method of  claim 35  wherein comparing the measure levels consists of Significance Analysis Of Mircoarrarys (SAM).