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

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• 作者：Liv Tybjæ ; rg Nordestgaard^a ; Anne Tybjæ ; rg-Hansen^a ; ^b ; ^c ; Bø ; rge G. Nordestgaard^b ; ^c ; ^d ; Ruth Frikke-Schmidt^a ; ^b ; ^c ; ^{ruth.frikke-schmidt@regionh.dk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Alzheimer's disease ; Cerebrovascular disease ; ATP-binding cassette transporter A1 ; Apolipoprotein E ; Blood-brain barrier
• 刊名：Alzheimer's & Dementia
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：11
• 期：12
• 页码：1430-1438
• 全文大小：1143 K

文摘

The 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.

bsSec_2">Methods

bspara0015">We 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.

bsSec_3">Results

bspara0020">N1800H 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.

bsSec_4">Discussion

bspara0025">A 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.