Related Experiment Video
Updated: Nov 1, 2025
Author Spotlight: Exploring Sex-Specific Glial Signatures and Therapeutic Leads for Alzheimer's Disease
Published on: May 20, 2024
Implications for microglial sex differences in tau-related neurodegenerative diseases
Yasmine V Doust1, Anna E King1, Jenna M Ziebell1
1Wicking Dementia Research and Education Centre, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia.
Abstract:
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.
Insights
Aging brains show detrimental changes in microglia, immune cells that worsen tau protein pathology in neurodegenerative tauopathies. These changes may differ between sexes, impacting disease progression.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Tauopathies are neurodegenerative diseases characterized by tau protein pathology.
- Neuroinflammation, mediated by microglia, exacerbates tau pathology and neurodegeneration.
- Aging alters microglia, leading to a pro-inflammatory state and loss of homeostatic functions.
Purpose of the Study:
- To review the interplay between age-related microglial dysfunction and tau pathology.
- To explore the implications of microglial sexual dimorphism in tauopathies.
Main Methods:
- Literature review focusing on neuroinflammation, microglia, aging, and tauopathies.
- Analysis of studies investigating microglial function and sex differences in neurodegeneration.
Main Results:
- Dysfunctional, aged microglia are associated with increased tau pathology.
- Sex differences in microglial function suggest varied roles in tauopathy development and progression.
Conclusions:
- A detrimental cycle exists between aging, microglial changes, and tau pathology.
- Understanding microglial sexual dimorphism is crucial for developing sex-specific tauopathy treatments.
