Uptake, degradation, and release of fibrillar and soluble forms of Alzheimer's amyloid β-peptide by microglial cells

Abstract

Microglia are phagocytic cells that are the main inflammatory response cells of the central nervous system. In Alzheimer's disease brain, activated microglia are concentrated in regions of compact amyloid deposits that contain the 39-43-amino acid Aβ peptide. We examined the uptake, degradation, and release of small aggregates of fibrillar Aβ (fAβ) or soluble Aβ (sAβ) by microglia. We found that although some degradation of fail was observed over 3 days, no further degradation was observed over the next 9 days. Instead, there was a slow release of intact Aβ. The poor degradation was not due to inhibition of lysosomal function, since the rate of α2-macroglobulin degradation was not affected by the presence of fail in the late endosomes/lysosomes. In contrast to faβ, internalization of sail was not saturable. After internalization, sAβ was released rapidly from microglia, and very little was degraded. These data show that fAβ and sAβ interact differently with microglia but that after internalization a large fraction of both are released without degradation.