Loss-of-Function PCSK9 Mutations Are Not Associated With Alzheimer Disease.

TitleLoss-of-Function PCSK9 Mutations Are Not Associated With Alzheimer Disease.
Publication TypeJournal Article
Year of Publication2018
AuthorsPaquette M, Saavedra YGrisel Lun, Poirier J, Théroux L, Dea D, Baass A, Dufour R
JournalJ Geriatr Psychiatry Neurol
Date Published2018 Mar

BACKGROUND: Hypercholesterolemia is a major risk factor for the late-onset form of Alzheimer disease (AD). Loss-of-function (LOF) mutations of PCSK9 and PCSK9 inhibitors lower low-density lipoprotein cholesterol (LDL-C) and have been associated with a reduced risk of cardiovascular disease. The aim of this study was to examine the effect of PCSK9 LOF variants on risk and age of onset of AD.METHODS: A total of 878 participants (410 controls and 468 AD cases) from the Quebec Founder Population were included in the study.RESULTS: Fifty-four (6.2%) participants carried the R46L mutation, whereas 226 (26.2%) participants carried the InsLEU mutation. There was no protective or no deleterious effect of carrying PCSK9 LOF mutations on AD prevalence nor on age of onset, even when stratified by apolipoprotein E epsilon 4 genotype or by gender.CONCLUSION: Our data indicate that carrying PCSK9 LOF mutations has a neutral effect on neurocognitive health and the prevalence of AD.

Alternate JournalJ Geriatr Psychiatry Neurol
PubMed ID29562810