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Volume 272, Number 46, Issue of November 14, 1997 pp. 29390-29397
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Slow Degradation of Aggregates of the Alzheimer's Disease Amyloid -Protein by Microglial Cells

(Received for publication, April 25, 1997, and in revised form, September 3, 1997)

Donata M. Paresce , Haeyong Chung ^§ and Frederick R. Maxfield

From the  Biochemistry Department, Cornell University Medical College, New York, New York 10021 and the ^§ Pathology Department, College of Physicians and Surgeons, Columbia University, New York, New York 10032

Microglia are immune system cells associated with senile plaques containing -amyloid (A) 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 that resemble those present in dense Alzheimer's disease plaques. In this study, we compared the degradation by microglia of A microaggregates with the degradation of two other proteins, acetylated low density lipoprotein and ₂-macroglobulin. We found that the majority of the internalized A in microaggregates was undegraded 72 h after uptake, whereas 70-80% of internalized acetylated low density lipoprotein or ₂-macroglobulin was degraded and released from cells in trichloroacetic acid-soluble form after 4 h. In the continued presence of fluorescent A microaggregates for 4 days, microglia took up huge amounts of A and became engorged with undigested material. These data suggest that microglia can slowly degrade limited amounts of A plaque material, but the degradation mechanisms can be overwhelmed by larger amounts of A.

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