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Summary Alzheimer’s disease is characterized by the deposition of extracellular amyloid-beta (Aβ) plaques. While microglial phagocytosis is a major mechanism through which Aβ is cleared, there is no method for quantitatively assessing Aβ phagocytic capacity of microglia in vivo. Here, we present a flow cytometry-based method for investigating the Aβ phagocytic capacity of microglia in vivo. This method enables the direct comparison of Aβ phagocytic capacity between different microglial subpopulations as well as the direct isolation of Aβ phagocytic microglia for downstream applications. For complete details on the use and execution of this protocol, please refer to Lau et al. (2020).

Quantitative in vivo assessment of amyloid-beta phagocytic capacity in an Alzheimer’s disease mouse model