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

• Published in: Journal of geriatric psychiatry and neurology Vol. 31; no. 2; p. 90
• Main Authors: Paquette, Martine, Saavedra, Yascara Grisel Luna, Poirier, Judes, Théroux, Louise, Dea, Doris, Baass, Alexis, Dufour, Robert
• Format: Journal Article
• Language: English
• Published: United States 01.03.2018
• Subjects: Age of Onset; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Cholesterol, LDL - blood; Female; Genotype; Genotyping Techniques - methods; Humans; Male; Middle Aged; Mutation; Polymorphism, Single Nucleotide; Proprotein Convertase 9 - blood; Proprotein Convertase 9 - genetics; Risk Factors; PCSK9; cholesterol; dementia; Alzheimer disease; LDL-C; human
• ISSN: 0891-9887
• DOI: 10.1177/0891988718764330

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. A total of 878 participants (410 controls and 468 AD cases) from the Quebec Founder Population were included in the study. 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. Our data indicate that carrying PCSK9 LOF mutations has a neutral effect on neurocognitive health and the prevalence of AD.