Manipulating Phagocyte Activity in Alzheimer's Disease

Abstract

Increased numbers of reactive microglia are a commonly described histological change in the brains of patients with Alzheimer’s disease and also in rodent models of disease [1–3]. These cells are often, but not always, reported in association with deposits of fibrillar amyloid-β (Aβ) peptide [4–7], and this proximity has helped support the idea that the microglia are responding to Aβ by acquiring a reactive phenotype. Data from rodent studies indicate that a more appropriate term may be phagocytes rather than microglia since some amount of blood-derived macrophage are intermingled with resident microglia around the amyloid plaques [8]. Regardless of the immediate origin of these cells, there has been little in situ evidence from either human or rodent brains that these phagocytic cells are capable of taking up the peptide during the typical disease process [9–11]. Indeed, numerous studies have attempted strategies to modulate the phenotype of brain phagocytic cells to facilitate their ability to clear the peptide. These strategies not only influenced infiltration of peripheral blood derived phagocytes but also