Implications for microglial sex differences in tau-related neurodegenerative diseases

Tauopathies are a group of neurodegenerative diseases that involve pathological changes to the tau protein. Neuroinflammation is a commonly reported feature of tauopathies that has been demonstrated to exacerbate tau pathology and, hence, neurodegeneration. Microglia can mediate the inflammatory response in order to maintain brain homeostasis. In the aged brain, microglia are reported to undergo morphological and functional changes, adopting a pro-inflammatory profile and loss of homeostatic functions. Dystrophic and dysfunctional microglia are associated with tau pathology in the healthy and diseased brain which is proposed to contribute to disease development and progression. Microglia have also been recently demonstrated to possess sexually dimorphic roles in the developing, adult and aged brain. The sex differences in microglial functionality suggest that microglia may contribute to tauopathies which may differ between sexes. This review highlights the detrimental loop between age-related microglial changes and tau pathology with implications for microglial sexual dichotomy. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

Tauopathies are a group of neurodegenerative diseases involving pathological changes to the tau protein. Neuroinflammation exacerbates tau pathology and neurodegeneration, with microglia mediating the inflammatory response. Age-related changes in microglia and tau pathology create a detrimental loop, while microglial sexual dichotomy may contribute differently to tauopathies in different sexes.