Journal
JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY
Volume 31, Issue 2, Pages 90-96Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0891988718764330
Keywords
Alzheimer disease; cholesterol; LDL-C; PCSK9; dementia; human
Categories
Funding
- Fondation Leducq Transatlantic Network of Excellence [13CVD03]
- Canadian Institute of Health Research
- J.L. Levesques Foundation
- Merck Frosst
- Amgen
- Astra Zeneca
- CIHR
- Fondation Leducq
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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.
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