“Serum proteomics reveals APOE dependent and independent protein signatures in Alzheimer’s disease.”
Elisabet Frick, et al. – Icelandic Heart Association, National Institute on Aging.
Background: High-quality data on serum proteins that could serve as biomarkers of future AD risk are scarce, as is knowledge of how the numerous genes affected by APOE could mediate the risk conferred by the APOE4 allele.
This Study: Using longitudinal data from the AGES Cohort (n=5,294), Frick and colleagues identified 329 proteins linked to risk of developing late-onset AD (LOAD). Of these, controlling for APOE carrier status found that 130 were statistically independent of APOE genotype, while 17 were dependent on carrier status. Curiously, for 3 proteins that were negatively linked with LOAD risk – the small GTPase ARL2, the calcium-binding protein S100A13, and the tubulin folding cofactor TBCA – controlling for APOE genotype reversed the association, becoming positively associated with disease risk, suggesting that APOE4 lowers their levels to the point of masking the positive link between them and LOAD.
Bottom Line: The proteins identified in this study may serve as key biomarkers or therapeutic targets. Moreover, the complex and potent role for APOE in LOAD requires that it must be controlled for when examining the association between other factors and AD risk.
