4.6 Review

The role of ATP-binding cassette subfamily A in the etiology of Alzheimer's disease

Journal

MOLECULAR NEURODEGENERATION
Volume 17, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s13024-022-00536-w

Keywords

ATP-binding cassette transporter; ABCA1; ABCA2; ABCA5; ABCA7; Alzheimer's disease; Amyloid beta; Cholesterol homeostasis

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Funding

  1. Flemish Government
  2. Flanders Impulse Program on Networks for Dementia Research

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This review provides a comprehensive overview of the contribution of the ABCA subfamily to the etiopathogenesis of AD. The genetic variants and functional abnormalities in these transporters have been found to be related to AD, and a better understanding of their function can contribute to the development of novel therapeutic strategies for AD.
Background: Alzheimer's disease (AD) is the leading cause of dementia, clinically characterized by memory deficits and progressive cognitive decline. Despite decades of research effective therapies are lacking, and a large part of the genetic heritability remains unidentified. ABCA7 and ABCA1, members of the ATP-binding cassette subfamily A (ABCA), were identified as AD risk genes in genome-wide association studies. Nevertheless, genetic and/or functional studies propose a link between AD and two other members of the ABCA subclass, i.e., ABCA2 and ABCA5. Main body: Changes in expression or dysfunction of these transporters were found to increase amyloid beta levels. This might be related to the common role of ABCA transporters in cellular cholesterol homeostasis, for which a prominent role in AD development has been suggested. In this review, we provide a comprehensive overview and discussion on the contribution of the ABCA subfamily to the etiopathogenesis of AD. Conclusions: A better understanding of the function and identification of disease-associated genetic variants in ABCA transporters can contribute to the development of novel therapeutic strategies for AD.

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