title: Loss-of-function mutation in ABCA1 and risk of Alzheimer's disease and cerebrovascular disease.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospitals, Copenhagen, Denmark.
authors.forename: Liv Tybjærg
authors.initials: LT
authors.lastname: Nordestgaard
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospitals, Copenhagen, Denmark; The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospitals, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjærg-Hansen
authors.affiliation: The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospitals, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospitals, Herlev, Denmark.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospitals, Copenhagen, Denmark; The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospitals, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: ruth.frikke-schmidt@regionh.dk.
authors.forename: Ruth
authors.initials: R
authors.lastname: Frikke-Schmidt
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001057:Apolipoproteins E / Q000097:blood*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D012042:Registries; D012307:Risk Factors
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E
keywords: ATP-binding cassette transporter A1; Alzheimer's disease; Apolipoprotein E; Blood-brain barrier; Cerebrovascular disease