Validation of non-amyloid, non-Tau CSF biomarkers for Alzheimer's disease

 
   Lead Investigator:    Umesh Gangishetti
   Institution      :    Emory
   E-Mail           :    umesh.gangishetti@emory.edu
   Proposal ID      :    883


   Publications:


1  Gangishetti U, Howell J, Perrin R, Louneva N, Watts K, Kollhoff A, Grossman M, Wolk D, Shaw L, Morris J, Trojanowski J, Fagan A, Arnold S, Hu W
   Non-beta-amyloid/tau cerebrospinal fluid markers inform staging and progression in Alzheimer's disease
   Journal Article  Alzheimers Res Ther,1:98,2018,PMC6156847

   PUBLISHED



2  Gangishetti U, Howell J, Perrin R, Morris J, Trojanowski J, Fagan A, Arnold S, Hu W
   CSF non-Beta-Amyloid, non-Tau Biomarkers for Clinical Alzheimer's Disease Stages
   Abstract  Neurology,90:S48.002,2018,

   PUBLISHED





   Proposal Description:
   Cerebrospinal fluid (CSF) biomarkers for Alzheimer?s disease (AD) have            significantly enhanced the accurate ante-mortem prediction of AD pathology even   when symptoms are very mild. CSF biomarkers for AD, including beta-amyloid 1-42   (Ab42), total Tau (t-Tau), and Tau phosphorylated at threonine 181 (p-Tau181),    reflect the pathologic substrate of AD, and their standardization and clinical    application in diagnosis represent a These biomarkers can now be used to match    drug- and placebo-treated subjects, and to enhance the power of the study by      creating a relatively homogeneous patient population.  However, these             biomarkers have a number of shortcomings.  CSF A#6153842 and t-Tau levels         often reach plateau levels before any mild clinical symptom is detectable,        which would make them poor markers in disease staging and progression             monitoring.  Furthermore, while CSF A#6153842 and t-Tau levels have been          correlated with increased risk of developing dementia within a certain time       frame (5 or 10 years) at the group level, there is no clear correlation between   their levels and the rates of cognitive decline at the individual level.  In      other words, altered CSF A#6153842 and t-Tau levels may inform IF but not         WHEN any subject may develop further cognitive deterioration.  Thus, there        persists an urgent need for non-amyloid, non-Tau biomarkers of AD for staging,    monitoring progression, and identifying response to drug therapies.  Here we      propose to leverage the clinical, neuropathological, and biomarker expertise      available at Emory University, University of Pennsylvania, and Washington         University at St. Louis to validate 12 previously identified non-amyloid,         non-Tau biomarkers in the CSF.  We will do this through independent assays for    the most promising CSF non-amyloid, non-Tau biomarkers, using banked CSF          samples from subjects with norma