**1. Introduction**

ATP-binding cassette (ABC) transporters are present in all living organisms. In humans, this family comprises 49 members that are classified based on their sequence homologies and their conserved nucleotide binding domains (NBDs) into seven subfamilies, designated from A to G. These transporters play a significant role by transporting ions, small organic or inorganic molecules, peptides, proteins and lipids from a cellular compartment to another one or across the cell membranes [1,2]. Importantly, their physiological functions strongly depend on their cellular localization (membrane, endoplasmic reticulum, Golgi, etc.) as well as the organ and cell type in which they are expressed. For example, members of the ABCB and ABCC subfamilies are expressed in physiological barriers such as intestine and blood–brain interfaces to restrict the entry or mediate the exit of harmful endogenous molecules or xenobiotics [3,4]. Overexpression of these ABC transporters has been reported in several cancers and is responsible for the multidrug resistance (MDR) phenotype of cancer cells [5]. Members of the ABCG and A subfamilies mediate cholesterol and lipid efflux from cells to low- or high-density lipoproteins and are highly expressed by cells involved in lipid homeostasis such as macrophages or hepatocytes.

It is therefore not surprising that ABC transporter deficiencies lead to major diseases including but not limited to atherosclerosis, cystic fibrosis or neurodegenerative diseases such as Alzheimer's disease (AD) [2,6,7]. AD is the most common form of dementia in the world. This disease is mainly characterized by brain atrophy as a consequence of the deposition of amyloid-β (Aβ) peptides and tau protein hyperphosphorylation and aggregation [8]. Since the early 2000s, several ABC transporters such as ABCB1, ABCA1, ABCG2, ABCC1 and ABCG4 are under scrutiny in AD because of their in vitro and in vivo involvement in Aβ peptide synthesis and/or its deposition. These different contributions in the AD field are already summarized elsewhere [4,7,9,10].

The ATP-Binding cassette transporter subfamily A member 7 (ABCA7) was first identified in the early 2000s [11]. As shown in Figure 1, ABCA7 was poorly studied until

**Citation:** Dib, S.; Pahnke, J.; Gosselet, F. Role of ABCA7 in Human Health and in Alzheimer's Disease. *Int. J. Mol. Sci.* **2021**, *22*, 4603. https:// doi.org/10.3390/ijms22094603

Academic Editor: Thomas Falguières

Received: 29 March 2021 Accepted: 26 April 2021 Published: 27 April 2021

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2011. These studies mainly investigated ABCA7 involvement in peripheral cholesterol metabolism and phagocytosis processes. In 2011, Hollingworth et al. highlighted a very strong association between ABCA7 polymorphisms and AD patients in a genome-wide association study (GWAS) [12].

**Figure 1.** Number of searchable publications in Pubmed per year by the terms specified in the legend. For the "ABCA7 + Alzheimer" search, a second analysis of the obtained publications was performed to exclusively select studies and review investigating the role of ABCA7 in AD. Data source: Pubmed. Search date 31/12/2020. Y-axis shows number of publications, X-axis shows years

Since then, the number of projects studying ABCA7 have been considerably increased, and almost all of them have been realized with the objective to decipher the molecular role of ABCA7 in AD (Figure 1).

This review aims to summarize the first roles of ABCA7 identified in the periphery, but also to describe the most recent findings demonstrating its significant contribution in brain functioning and in AD onset and development.
