Investigator Names and Contact Information
Susan Resnick and Steve Rapp
Introduction/Intent
We propose to conduct a coordinated investigation in WHIMS of blood-based markers that may provide mechanistic insights into factors underlying cognitive resilience despite the presence of one or more APOE e4 genetic risk allele(s) for AD ("APOE escapees" as described by Allison Goate). We will focus on pathways that have been considered in relation to risk for AD to determine physiologic profiles at WHI baseline in women who maintain cognitive health through old age versus those who develop cognitive impairment. We will measure markers of insulin resistance, inflammation, and auto-antibody production, and perform targeted metabolomics assays, including lipodomics. Assays will be performed for 709 e4 carriers (359 women who develop impairment and 350 who remain free of cognitive impairment, excluding the e2/e4 individuals due to low number) and a similar number of individuals with the e3/e3 genotype (566 who develop impairment and 350 who remain free of cognitive impairment).
Key Questions and Contrasts:
