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

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 A beta peptide. We examined the uptake, degradation, and release of small aggregates of fibrillar A beta (fA beta) or soluble A beta (sA beta) by microglia, We found that although some degradation of fA beta was observed over 3 days, no further degradation was observed over the next 9 days, Instead, there was a slow release of intact A beta. The poor degradation was not due to inhibition of lysosomal function, since the rate of alpha 2-macroglobulin degradation was not affected by the presence of fA beta in the late endosomes/lysosomes. In contrast to fA beta, internalization of sA beta was not saturable. After internalization, sA beta was released rapidly from microglia, and very little was degraded. These data show that fA beta and sA beta interact differently with microglia but that after internalization a large fraction of both are released without degradation.