Method of diagnosing, preventing and/or treating dementia & related disorders

Abstract

Described are assay methods, modules and kits useful in the detection, treatment and/or prevention of dementia and related conditions, including but not limited to Alzheimer's disease and mild cognitive disorders.

1 . A method for diagnosing Alzheimer's-related dementia in a patient comprising (a) obtaining a test sample from a patient; (b) measuring a level of a first biomarker in said test sample, wherein said first biomarker comprises Aβ 16, Aβ 17, or combinations thereof; and (c) diagnosing from said measuring step the presence, absence, and/or progression of Alzheimer's-related dementia in said patient. 
     
     
         2 . The method of  claim 1  wherein said method further comprises measuring a level of at least one additional biomarker in said sample and determining from said level of said first biomarker and said level of said at least one additional biomarker the presence, absence, and/or progression of Alzheimer's-related dementia in said patient. 
     
     
         3 . The method of  claim 2  wherein said method further comprises comparing said level of said first biomarker and said at least one additional biomarker(s) in said sample to a level of said first biomarker and said at least one additional biomarker(s) in a normal control sample and diagnosing the presence, absence and/or progression of Alzheimer's-related dementia in said patient based on said comparison. 
     
     
         4 . The method of  claim 2  wherein said at least one additional biomarker comprises Aβ 42, Aβ 40, Aβ 38, Aβ 39, Aβ 37, Aβ 34, Aβ 43, total tau, P-tau, C-tau, or combinations thereof. 
     
     
         5 . The method of  claim 1  further comprising conducting a PET scan of said patient's brain using a radioactive diagnostic agent to estimate plaque density in said patient, and said diagnosing step further comprises diagnosing the presence, absence, and/or progression of Alzheimer's-related dementia in said patient based on said PET scan and said biomarker levels. 
     
     
         6 . The method of  claim 5  wherein said radioactive diagnostic agent is Amyvid, Pittsburgh Compound B, or combinations thereof. 
     
     
         7 . A method for monitoring the disease progression of and/or efficacy of a treatment regimen for Alzheimer's-related dementia in a patient, said method comprising (a) obtaining two or more test samples from a patient undergoing said treatment regimen for Alzheimer's-related dementia, wherein said two or more test samples include (i) a first test sample obtained from said patient at time t and (ii) at least one additional test sample obtained at time (t+n), wherein n is an integer greater than 1; (b) measuring the level(s) of a first biomarker in said two or more test samples, wherein said first biomarker comprises Aβ 16, Aβ 17, or combinations thereof; and (c) determining from said level(s) of said first biomarker the progression of and/or efficacy of said treatment regimen in said patient. 
     
     
         8 . The method of  claim 7  wherein said method further comprises measuring a level of at least one additional biomarker in said two or more test samples and determining from said level(s) of said first biomarker and said at least one additional biomarker the disease progression and/or efficacy of said treatment regimen for Alzheimer's-related dementia in said patient. 
     
     
         9 . The method of  claim 8  wherein said method further comprises comparing said level(s) of said first biomarker and said at least one additional biomarker(s) in said two or more test samples to a level(s) of said first biomarker and said at least one additional biomarker(s) in a normal control sample and determining said disease progression and/or treatment efficacy based on said comparison. 
     
     
         10 . The method of  claim 8  wherein said at least one additional biomarker comprises Aβ 42, Aβ 40, Aβ 38, Aβ 39, Aβ 37, Aβ 34, Aβ 43, total tau, P-tau, C-tau, or combinations thereof. 
     
     
         11 . The method of  claim 8  further comprising conducting a PET scan of said patient's brain using a radioactive diagnostic agent to estimate plaque density in said patient, and said diagnosing step further comprises diagnosing disease progression and/or treatment efficacy based on said PET scan and said biomarker levels. 
     
     
         12 . The method of  claim 11  wherein said radioactive diagnostic agent is Amyvid, Pittsburgh Compound B, or combinations thereof. 
     
     
         13 . A method for detecting plaques in the brain of a patient, said method comprising (a) obtaining two or more test samples from a patient undergoing a treatment regimen for dementia, wherein said two or more test samples include (i) a first test sample obtained from said patient at time t and (ii) at least one additional test sample obtained at time (t+n), wherein n is an integer greater than 1; (b) measuring the level(s) of a first biomarker in said two or more test samples, wherein said first biomarker comprises Aβ 16, Aβ 17, Aβ 42, Aβ 40, Aβ 38, Aβ 39, Aβ 37, Aβ 34, Aβ 43, total tau, P-tau, C-tau, or combinations thereof; and (c) determining from said level(s) of said first biomarker the presence and/or absence of plaques in the brain of said patient. 
     
     
         14 . The method of  claim 13  wherein said method further comprises measuring a level of at least one additional biomarker in said two or more test samples, wherein said additional biomarker comprises Aβ 16, Aβ 17, Aβ 42, Aβ 40, Aβ 38, Aβ 39, Aβ 37, Aβ 34, Aβ 43, total tau, P-tau, C-tau, or combinations thereof, and determining from said level(s) of said first biomarker and said level(s) of said at least one additional biomarker the presence and/or absence of plaques in the brain of said patient. 
     
     
         15 . The method of  claim 14  wherein said method further comprises comparing said level(s) of said first biomarker and said at least one additional biomarker(s) in said two or more test samples to a level of said first biomarker and said at least one additional biomarker(s) in a normal control sample and determining the presence and/or absence of plaques in the brain of said patient based on said comparison. 
     
     
         16 . A method for diagnosing Alzheimer's-related dementia and/or plaque formation in a patient comprising (a) obtaining a test sample from a patient; (b) measuring a level of an autoantibody to a first biomarker in said test sample, wherein said first biomarker is an A-beta peptide, tau, a fragment or isoform of an A-beta peptide or tau, or combinations thereof; (c) diagnosing from said measuring step the presence, absence, and/or progression of Alzheimer's-related dementia and/or plaque formation in said patient. 
     
     
         17 . The method of  claim 16  wherein said autoantibody binds to an A-beta peptide or a fragment or isoform thereof. 
     
     
         18 . The method of  claim 17  wherein said autoantibody binds to an A-beta peptide selected from the group consisting of Aβ 42, Aβ 40, Aβ 38, Aβ 39, Aβ 37, Aβ 34, Aβ 43, Aβ 16, Aβ 17 or combinations thereof. 
     
     
         19 . The method of  claim 16  wherein said autoantibody binds to tau or a fragment or isoform thereof. 
     
     
         20 . The method of  claim 19  wherein said autoantibody binds to a tau protein selected from total tau, P-tau, C-tau, or combinations thereof. 
     
     
         21 . The method of  claim 16  wherein said method further comprises measuring a level of an additional autoantibody to at least one supplemental biomarker in said sample, wherein said supplemental biomarker comprises one or more of the following: an Aβ peptide, tau, a fragment or isoform of an Aβ peptide or tau, or combinations thereof, and said first biomarker and said supplemental biomarker are different, and determining from said levels of autoantibody and additional autoantibody the presence, absence, and/or progression of Alzheimer's-related dementia and/or plaque formation in said patient. 
     
     
         22 . The method of  claim 21  wherein said method further comprises comparing said levels of autoantibody and additional autoantibody in said sample to levels of autoantibody and additional autoantibody in a normal control sample and diagnosing the presence, absence and/or progression of Alzheimer's-related dementia and/or plaque formation in said patient based on said comparison. 
     
     
         23 . The method of  claim 21  wherein said at least one additional biomarker comprises A-beta peptide or a fragment or isoform thereof. 
     
     
         24 . The method of  claim 23  wherein said A-beta peptide is selected from the group consisting of Aβ 42, Aβ 40, Aβ 38, Aβ 39, Aβ 37, Aβ 34, Aβ 43, Aβ 16, Aβ 17 or combinations thereof. 
     
     
         25 . The method of  claim 21 , wherein said at least one additional biomarker comprises tau or a fragment or isoform thereof. 
     
     
         26 . The method of  claim 25  wherein said at least one additional biomarker is selected from the group consisting of total tau, P-tau, C-tau, or combinations thereof. 
     
     
         27 . The method of  claim 16  further comprising conducting a PET scan of said patient's brain using a radioactive diagnostic agent to estimate plaque density in said patient, and said diagnosing step further comprises diagnosing the presence, absence, and/or progression of Alzheimer's-related dementia and/or plaque formation in said patient based on said PET scan and said autoantibody levels. 
     
     
         28 . The method of  claim 27  wherein said radioactive diagnostic agent is Amyvid, Pittsburgh Compound B, or combinations thereof.