ABCA7 haplodeficiency disturbs microglial immune responses in the mouse brain

Alzheimer's disease (AD), characterized by progressive neurodegeneration and brain accumulation of amyloid-β (Aβ) and tau, is the leading cause of dementia in the elderly. While increasing genetic studies have demonstrated that loss-of-function variants in ABCA7 are associated with AD risk, the mechanisms of their pathogenic contributions are not well understood. Here we show that ABCA7 haplodeficiency compromises microglial responses by impairing CD14 expression on acute lipopolysaccharide stimulation in mouse models. Furthermore, in the presence of amyloid pathology, ABCA7 haplodeficiency leads to excessive microglial Aβ accumulation accompanied by increased endosomal compartments. Our findings suggest that ABCA7 loss of function is involved in the development and progression of AD by causing microglial dysregulation.