Enlargement of Aβ aggregates through chemokine-dependent microglial clustering

Abstract

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 (Aβ)-induced BV-2 microglia to form clusters. The recruitment of BV-2 microglia bearing membrane-adhered Aβ enlarged preexisting Aβ aggregates. The receptors involved in the microglial uptake of Aβ, including integrin, formyl peptide like receptor 1, and scavenger receptors, also mediated the microglial clustering. Neutralization antibodies against chemokines significantly attenuated Aβ-induced microglial clustering and the enlargement of Aβ aggregates. Our results reveal a novel role of microglia in directly increasing the size of Aβ aggregates and suggest the targeting of Aβ-mediated microglial chemotactic migration in developing therapeutic interventions for AD.