Slow degradation of aggregates of the Alzheimer's disease amyloid beta-protein by microglial cells

Microglia are immune system cells associated with senile plaques containing beta-amyloid (A beta) in Alzheimer's disease, Although microglia are an integral part of senile plaques, their role in the development of Alzheimer's disease is not known, Because microglia are phagocytic cells, it has been suggested that microglia may function as plaque-attacking scavenger cells, Microglia bind and internalize microaggregates of A beta that resemble those present in dense Alzheimer's disease plaques. In this study, we compared the degradation by microglia of A beta microaggregates with the degradation of two other proteins, acetylated low density lipoprotein and alpha(2)-macroglobulin. We found that the majority of the in internalized A beta in microaggregates was undegraded 72 h after uptake, whereas 70-80% of internalized acetylated low density lipoprotein or alpha(2)-macroglobulin was degraded and released from cells in trichloroacetic acid-soluble form after 4 h, In the continued presence of fluorescent A beta microaggregates for 4 days, microglia took up huge amounts of A beta and became engorged with undigested material, These data suggest that microglia can slowly degrade limited amounts of A beta plaque material, but the degradation mechanisms can be overwhelmed by larger amounts of A beta.