Impact of APOE e2 on Neuropathology: Beyond Amyloid and Tau

 
   Lead Investigator:    Terry Goldberg
   Institution      :    Columbia University Medical Center
   E-Mail           :    Terry.Goldberg@nyspi.columbia.edu
   Proposal ID      :    1054



   Proposal Description:
   APOE is the major lipid transporter in brain. It is triallelic. e2 reduces risk of AD (OR=.54) while e4 increases risk of AD (OR.3.50) when compared to the neutral variant e3.  e2 is also associated with longevity. Despite its clear role in neuroprotection, it is under-researched. While an anti-AD CSF profile for Abeta and p-tau has been observed, there have been few studies of these molecules in tissue. Here we will directly assess the  impact of e2 on various neuropathologies in a large sample of NACC post mortem brains.  Aim 1. We will examine the role of e2 genotype in reductions of amyloid plaques in tau NFTs in A. non-AD non-demented cases and B. in AD, demented cases.  Aim 2. We will examine the role of e2 genotype in reductions of non-Ad pathologies, including TDP-43, hippocampal sclerosis, Lewy bodies, and cerebrovascular disease.  Aim 3. We will examine the impact of e2 on demographic factors (age, education) and cognition over time.