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Cited by 139Alzheimer's disease research and treatmentsLipoproteins and Cardiovascular HealthDementia and Cognitive Impairment Research

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

Nordestgaard, Liv Tybjærg, Tybjærg‐Hansen, Anne, Nordestgaard, Børge G., Frikke‐Schmidt, Ruth·2015·Alzheimer's & Dementia
DOI 10.1016/j.jalz.2015.04.006
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Abstract

Introduction: 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. Discussion: 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.

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Crossref · 10.1016/j.jalz.2015.04.006

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  • ICVD diagnoses were validated by trained physicians using WHO definitions of cerebrovascular disease.

    “Possible cerebrovascular events (hospitalized and non-hospitalized) were validated by trained physicians using the WHO definitions of cerebrovascular disease, as previously described [34].”

    From APOE and vascular disease: Sequencing and genotyping in general population cohorts (2023) · cites this paper as [34]

  • In the general population, a loss-of-function mutation in ABCA1 is associated with low levels of apoE and increased risk of Alzheimer disease.

    “In the general population, a loss-of-function mutation in ABCA1 has been shown to be associated with low levels of apoE and increased risk of Alzheimer disease [79].”

    From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [79]

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Authors
Nordestgaard, L. T., Tybjærg‐Hansen, A., Nordestgaard, B. G., & Frikke‐Schmidt, R.
Affiliations
University of Copenhagen (DK)
Corresponding author
Frikke‐Schmidt, Ruth
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2015-06-13
Volume
11
Issue
12
Pages
1430-1438
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1016/j.jalz.2015.04.006
OpenAlex
W993364412
Cited by
139
References
12
Citations by year
2026: 4 · 2025: 13 · 2024: 19 · 2023: 9 · 2022: 13 · 2021: 21 · 2020: 14 · 2019: 14 · 2018: 7 · 2017: 13 · 2016: 10 · 2015: 2
FWCI
7.85
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Alzheimer s & Dementia (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • Sundhed og Sygdom, Det Frie Forskningsråd (10‐081618)
  • Gentofte Hospital
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
ABCA1
MeSH terms
Alzheimer Disease, Apolipoproteins E, Blood-Brain Barrier, Brain, Cerebrovascular Disorders, Female, Humans, Male, Mutation, Registries, Risk Factors, Amyloid beta-Peptides, ATP Binding Cassette Transporter 1

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