Impaired microglia clearance of beta-amyloid (Aβ) is implicated in the pathophysiology of AD and strategies to enhance clearance of AD pathology are being actively pursued by biopharma. Therefore, we examined whether iMGLs can phagocytose Aβ or tau, two hallmark AD pathologies. Like primary microglia, iMGLs internalize fluorescently labeled fibrillar Aβ (Figure 4B). iMGLs also recognize and internalize pHrodo-labled brain–derived tau oligomers (BDTOs) (Figure 4B). Fluorescence emitted indicates trafficking of pHrodo-conjugated BDTOs to the acidic lysosomal compartment showing that iMGLs can actively ingest extracellular tau that may be released during neuronal cell death (Villegas-Llerena et al., 2015) and support recent findings that microglia may play a role in tau propagation in AD and other tauopathies (Asai et al., 2015). Together, these findings suggest that iMGLs could be utilized to identify compounds in high-throughput drug-screening assays that enhance Aβ degradation or block exosome-mediated tau release.
