Genetics
A protective CETP variant buffers the memory-decline effect of APOE4 in older adults (Neurobiol Aging 2016)
Original title: Cholesteryl ester transfer protein genotype modifies the effect of apolipoprotein ε4 on memory decline in older adults
Since the CETP I405V polymorphism is separately associated with slower memory decline and lower Alzheimer's disease risk, researchers tested whether the favourable CETP V405 allele could buffer the harmful effect of the APOE4 risk allele on memory decline. Among 909 community-dwelling, nondemented older adults (aged 70 and above) from the Einstein Aging Study, episodic memory was tracked using a picture version of the Free and Cued Selective Reminding Test, revealing a significant APOE by CETP interaction on decline (P equals 0.01). APOE4 carriers declined faster than noncarriers among CETP I405I homozygotes (P equals 0.007) and I405V heterozygotes (P equals 0.015), but not among CETP V405V homozygotes (P equals 0.614), indicating the CETP V405 allele buffers APOE4-associated memory decline in a gene-dose-dependent manner.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.