Genetics
A well-powered Mendelian randomization study finds CETP-driven HDL cholesterol is not associated with Alzheimer's disease risk (Alzheimers Dement 2018)
Original title: Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease
Because evidence is conflicting on whether HDL cholesterol affects Alzheimer's disease risk, researchers used ten single nucleotide polymorphisms within the CETP locus that predict HDL cholesterol as genetic instruments, applying them to International Genomics of Alzheimer's Project exome chip data from up to 16,097 late-onset Alzheimer's disease cases and 18,077 cognitively normal elderly controls. Instrumental variable analyses using inverse variance weighting, weighted median, and MR-Egger methods found no association between genetically predicted HDL cholesterol and Alzheimer's disease risk (P greater than .7). The authors conclude their study does not support a role for HDL cholesterol altered via CETP in Alzheimer's disease risk, though it does not rule out other mechanisms by which HDL cholesterol could affect the disease.
Original abstract
Introduction: There is conflicting evidence whether high-density lipoprotein cholesterol (HDL-C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered HDL-C. We aimed to assess AD risk by genetically predicted HDL-C.
Methods: Ten single nucleotide polymorphisms within the CETP locus predicting HDL-C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR-Egger.
Results: Based on 10 single nucleotide polymorphisms distinctly predicting HDL-C in the CETP locus, we found that HDL-C was not associated with risk of AD (P > .7).
Discussion: Our study does not support the role of HDL-C on risk of AD through HDL-C altered by CETP. This study does not rule out other mechanisms by which HDL-C affects risk of AD.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.