TREM2 Ameliorates Neuronal Tau Pathology Through Suppression of Microglial Inflammatory Response

In this study, by employing a microglial-neuronal co-culture model, we showed that microglial inflammatory response induced by lipopolysaccharide led to tau hyperphosphorylation in neuronsvia activation of a major tau kinase glycogen synthase kinase 3 β, confirming the pathogenic effects of activated microglia on the progression of tau pathology. More importantly, by manipulating TREM2 levels in microglia with a lentiviral-mediated strategy, we demonstrated that TREM2 ameliorated the pathological effects of activated microglia on neuronal tau hy perphosphorylationvia suppression of microglial inflammatory response. Taken together, these findings uncover the underlying mechanisms by which TREM2 protects against tau pathology and highlight TREM2 as a potential therapeutic target for AD.
Source: Inflammation - Category: Allergy & Immunology Source Type: research