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

Microglia are widely held to play important pathophysiologic roles in Alzhe imer'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 mi croglial chemotaxis, phagocytosis, and secretory activity have common, tigh tly linked soluble intermediaries (e.g., cytokines, chemokines), cell surfa ce intermediaries (e.g., receptors, opsonins), and stimuli (e.g., highly in ert AP deposits and exposed neurofibrilly tangles), the mechanisms for micr oglial clearance of AP are necessarily coupled to localized inflammatory me chanisms that can be cytotoxic to nearby tissue. This presents a critical d ilemma for strategies to remove AP by enhancing micoglial activation-a dile mma that warrants substantial further investigation. (C) 2001 Elsevier Scie nce Ltd. All rights reserved.