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

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, membe...

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Detalles Bibliográficos
Autores principales: Bossaerts, Liene, Cacace, Rita, Van Broeckhoven, Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044696/
https://www.ncbi.nlm.nih.gov/pubmed/35477481
http://dx.doi.org/10.1186/s13024-022-00536-w
Descripción
Sumario: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 β 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.