Cholesteryl ester transfer protein genotype modifies the effect of apolipoprotein ε4 on memory decline in older adults

Apolipoprotein ε4 (ApoE4) is a strong genetic risk factor for sporadic Alzheimer's disease and memory decline in older adults. A single-nucleotide polymorphism in the cholesteryl ester transfer protein (CETP) gene (isoleucine to valine; V405) is associated with slower memory decline and a lower risk of Alzheimer's disease. As both genes regulate cholesterol, we hypothesized that the favorable CETPV405 allele may buffer the effect of ApoE4 on memory decline in older adults. Using linear regression, we examined the interactive effect of ApoE4 by CETPV405 on memory decline among 909 community-dwelling, nondemented, older adults (≥70 years) from the Einstein Aging Study. Episodic memory was measured using the picture version of the Free and Cued Selective Reminding Test with immediate recall (pFCSRT+IR). There was a significant ApoE × CETP interaction on decline in pFCSRT+IR scores (p = 0.01). ApoE4 carriers experienced faster decline than noncarriers among CETPI405I homozygotes (p = 0.007) and in CETPI405V heterozygotes (p = 0.015) but not in CETPV405V homozygotes (p = 0.614). Results suggest that the CETPV405 allele buffers ApoE4-associated memory decline in a gene dose-dependent manner.