Microglial chemotactic signaling factors in Alzheimer's disease.

The net migration of microglia induced by deposits of amyloid beta (Aβ) constitutes a chemotactic response of resident neuroimmune brain cells. This process serves to localize clusters of microglia nearby Aβ deposits preparatory to cellular activation and functional responses. Microglial responses to Aβ deposits localized in brain parenchyma and in blood vessels lead to acute and chronic neuroinflammation in Alzheimer's disease (AD) brain. This review summarizes studies on the prominent chemotactic factors MCP-1, MIP-1α and IL-8 and also includes recent work indicating VEGF and fractalkine as chemotactic agents. The possibility that microglial release of MCP-1 may play a role in mediating chemotactic responses of neural progenitor cells is also considered. The plethora of chemotactic factors and their cognate receptors suggests the utility in testing pharmacological modulation of chemotaxis for effects to inhibit chronic neuroinflammation and confer neuroprotection in AD animal models.