Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model

Microglia contain Aβ aggregates in AD mouse models and humans

The aggregation of Aβ is an initial step in the formation of plaques, requiring an acidic pH¹³ and micromolar concentrations of Aβ monomers¹⁴. The extracellular space does not meet these requisite conditions, suggesting that Aβ aggregation originates elsewhere. In contrast to the extracellular space, microglial lysosomes provide a suitable environment to facilitate Aβ aggregation, potentially contributing to the onset of plaque pathology¹⁵. To investigate the potential for microglia-mediated plaque formation, we examined Aβ aggregates within microglia in transgenic mouse models of AD. In 15-month-old 3xTg-AD mice, a time point at which plaques are beginning to form, we stained tissue for Thio-S (aggregated Aβ), microglia, and lysosomes. While plaque-associated microglia show accumulation of aggregates within their…