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Activated microglia mitigate Aβ-associated tau seeding and spreading
Maud Gratuze 1 2 3, Yun Chen 1 4 2 3, Samira Parhizkar 1 2 3, Nimansha Jain 1 2 3, Michael R Strickland 1 2 3, Javier Remolina Serrano 1 2 3, Marco Colonna 4 2 3, Jason D Ulrich 1 2 3, David M Holtzman 1 2 3
Abstract:
...Microglial repopulation in aged mice improved cognitive and neuronal deficits. In the context of AD pathology, we asked whether microglial removal and repopulation decreased Aβ-driven tau seeding and spreading. We show that both TREM2KO and microglial ablation dramatically enhance tau seeding and spreading around plaques. Interestingly, although repopulated microglia clustered around plaques, they had a reduction in disease-associated microglia (DAM) gene expression and elevated tau seeding/spreading. Together, these data suggest that TREM2-dependent activation of the DAM phenotype is essential in delaying Aβ-induced pathological tau propagation.
