The role of Abca7 in late‐onset Alzheimer’s disease animal models

Alzheimer's disease (AD) and other neurodegenerative diseases are typified by a robust microglial‐mediated immune response. Genetic studies have demonstrated that variants in microglial genes are linked to risk for AD. Genome‐wide association studies (GWAS) originally identified ATP‐binding cassette, sub‐family A, member 7 (ABCA7), as a novel risk gene of Alzheimer's disease (AD). Since then, accumulating evidence from in vitro, in vivo, and human‐based studies has extended this association, promoting ABCA7 as one of the most important risk genes of late‐onset AD (LOAD), harboring both common and rare risk variants with relatively large effect on AD risk. Besides associations with disease status, genetic and epigenetic ABCA7 markers show significant correlations with AD endophenotypes; in particular amyloid deposition and brain morphology. In conclusion, human‐based ‐omics studies provide converging evidence of (partial) ABCA7 loss as an AD pathomechanism.