Microglial chemotaxis, activation, and phagocytosis of amyloid β-peptide as linked phenomena in Alzheimer's disease

Microglia are widely held to play important pathophysiologic roles in Alzheimer's disease (AD). On exposure to amyloid beta peptide (AP) they exhibit chemotactic. phagocytic, phenotypic and secretory responses consistent with scavenger cell activity in a localized inflammatory setting. Because AD microglial chemotaxis, phagocytosis, and secretory activity have common, tightly linked soluble intermediaries (e.g., cytokines, chemokines), cell surface intermediaries (e.g., receptors, opsonins), and stimuli (e.g., highly inert AP deposits and exposed neurofibrilly tangles), the mechanisms for microglial clearance of AP are necessarily coupled to localized inflammatory mechanisms that can be cytotoxic to nearby tissue. This presents a critical dilemma for strategies to remove AP by enhancing micoglial activation-a dilemma that warrants substantial further investigation. (C) 2001 Elsevier Science Ltd. All rights reserved.