Clearance of amyloid-β peptides by microglia and macrophages: the issue of what, when and where

Accumulation of senile plaques consisting of amyloid-beta peptide (Ab) aggregates is a prominent pathological feature in Alzheimer's disease. Effective clearance of Ab from the brain parenchyma is thought to regulate the development and progression of the disease. Macrophages in the brain play an important role in Ab clearance by a variety of phagocytic and digestive mechanisms. Subpopulations of macrophages are heterogeneous such that resident microglia in the parenchyma, blood macrophages infiltrating from the periphery and perivascular macrophages residing along cerebral vessels make functionally distinct contributions to A beta clearance. Despite phenotypic similarities between the different macrophage subsets, a series of in vivo models have been derived to differentiate their relative impacts on A beta dynamics as well as the molecular mechanisms underlying their activities. This review discusses the key findings from these models and recent research efforts to selectively enhance macrophage clearance of A beta.