How microglia degrade large Alzheimer’s amyloid-beta plaques?
Microglia normally clears the amyloid beta plaques via phagocytosis but how larger fibrillar plaques that cannot be phagocytosed are digested is not known.
The researchers show that microglia use digestive exophagy to engage large Ab deposits that cannot be phagocytosed, forming acidic extracellular compartments on the aggregates into which lysosomal enzymes are exocytosed. The PI3K-AKT pathway modulates this process.
Microglia also exocytose intralysosomal undigested fibrillar Ab toward extracellular aggregates, potentially contributing to plaque growth.
https://www.cell.com/cell-reports/fulltext/S2211-1247(24)01403-7
