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. 2018 Sep 22:10:595-598.
doi: 10.1016/j.dadm.2018.08.008. eCollection 2018.

Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

Gina M Peloso  1 , Sven J van der Lee  2 ; International Genomics of Alzheimer's Project (IGAP); Anita L Destefano  1   3   4 , Sudha Seshardi  3   4   5
Collaborators, Affiliations

Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

Gina M Peloso et al. Alzheimers Dement (Amst). .

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.

Keywords: Cholesteryl ester transfer protein; Genetics; HDL-C; Instrumental variables; Single nucleotide polymorphisms.

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