Microfluidic chemotaxis platform for differentiating the roles of soluble and bound amyloid-? on microglial accumulation.

ABSTRACT: Progressive microglial accumulation at amyloid-? (A?) plaques is a well-established signature of the pathology of Alzheimer's disease, but how and why microglia accumulate in the vicinity of A? plaques is unknown. To understand the distinct roles of A? on microglial accumulation, we quantified microglial responses to week-long lasting gradients of soluble A? and patterns of surface-bound A? in microfluidic chemotaxis platforms. We found that human microglia chemotaxis in gradients of soluble A?42 was most effective at two distinct concentrations of 23?pg.mL(-1) and 23?ng.mL(-1) A?42 in monomers and oligomers. We uncovered that while the chemotaxis at higher A? concentrations was exclusively due to A? gradients, chemotaxis at lower concentrations was enhanced by A?-induced microglial production of MCP-1. Microglial migration was inhibited by surface-bound A?42 in oligomers and fibrils above 45?pg.mm(-2). Better understanding of microglial migration can provide insights into the pathophysiology of senile plaques in AD.

SUBMITTER: Cho H 

PROVIDER: S-EPMC3650586 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature