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. 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. 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.

中文翻译：

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ATP 结合盒亚家族 A 在阿尔茨海默病病因学中的作用

阿尔茨海默病 (AD) 是痴呆症的主要原因，其临床特征是记忆缺陷和进行性认知衰退。尽管进行了数十年的研究，但仍缺乏有效的治疗方法，并且很大一部分遗传性仍未确定。ATP 结合盒亚家族 A (ABCA) 的成员 ABCA7 和 ABCA1 在全基因组关联研究中被确定为 AD 风险基因。然而，遗传和/或功能研究提出了 AD 与 ABCA 亚类的两个其他成员，即 ABCA2 和 ABCA5 之间的联系。发现这些转运蛋白的表达或功能障碍的变化会增加淀粉样蛋白 β 的水平。这可能与 ABCA 转运蛋白在细胞胆固醇稳态中的共同作用有关，因此已经提出在 AD 发展中的重要作用。在本次审查中，我们对 ABCA 亚家族对 AD 发病机制的贡献进行了全面的概述和讨论。更好地了解 ABCA 转运蛋白中与疾病相关的遗传变异的功能和鉴定有助于开发新的 AD 治疗策略。