Enlargement of Aβ aggregates through chemokine-dependent microglial clustering

The number of microglia surrounding senile plaques is correlated with the size of plaques in Alzheimer's disease (AD). It is unclear whether more microglia are passively recruited toward larger senile plaques or, conversely, microglia recruited to senile plaques directly contribute to the growth of plaques. In this study, BV-2 microglia were used to delineate the role of microglia in the growth of plaques using time-lapse recording. Aggregated beta amyloid peptide (A beta)-induced BV-2 microglia to form clusters. The recruitment of BV-2 microglia bearing membrane-adhered A beta enlarged preexisting A beta aggregates. The receptors involved in the microglial uptake of A beta, including integrin, formyl peptide like receptor 1, and scavenger receptors, also mediated the microglial clustering. Neutralization antibodies against chemokines significantly attenuated A beta-induced microglial clustering and the enlargement of A beta aggregates. Our results reveal a novel role of microglia in directly increasing the size of A beta aggregates and suggest the targeting of A beta-mediated microglial chemotactic migration in developing therapeutic interventions for AD. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.