Loss‐of‐function mutation in ABCA1 and risk of Alzheimer's disease and cerebrovascular disease

Alzheimer's & Dementia - Tập 11 - Trang 1430-1438 - 2015
Liv Tybjærg Nordestgaard1, Anne Tybjærg-Hansen1,2,3, Børge G. Nordestgaard2,3,4, Ruth Frikke-Schmidt1,2,3
1Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospitals, Copenhagen, Denmark
2The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospitals, Herlev, Denmark
3Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
4Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospitals, Herlev, Denmark

Tóm tắt

AbstractIntroductionThe adenosine triphosphate‐binding cassette transporter A1 (ABCA1) is a major cholesterol transporter highly expressed in the liver and brain. In the brain, ABCA1 lipidates apolipoprotein E (apoE), facilitates clearance of amyloid‐β, and may be involved in maintenance of the blood‐brain barrier via apoE‐mediated pathways.MethodsWe tested whether a loss‐of‐function mutation in ABCA1, N1800H, is associated with plasma levels of apoE and with risk of Alzheimer's disease (AD) in 92,726 individuals and with risk of cerebrovascular disease in 64,181 individuals.ResultsN1800H AC (0.2%) versus AA (99.8%) was associated with a 13% lower plasma level of apoE (P = 1 × 10−11). Multifactorially adjusted hazard ratios for N1800H AC versus AA were 4.13 (95% confidence interval, 1.32–12.9) for AD, 2.46 (1.10–5.50) for cerebrovascular disease, and 8.28 (2.03–33.7) for the hemorrhagic stroke subtype.DiscussionA loss‐of‐function mutation in ABCA1, present in 1:500 individuals, was associated with low plasma levels of apoE and with high risk of AD and cerebrovascular disease in the general population.

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Alzheimer's & Dementia

Tập 11

1430-1438

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