Investigating the Effects of Glial Subtype-Specific Tau Expression in Drosophila melanogaster



Journal Title

Journal ISSN

Volume Title



Tauopathies are a diverse group of neurodegenerative diseases characterized by the aggregation of a microtubule-associated protein, tau. Recent studies have revealed that a subset of tauopathies can be classified by tau aggregation primarily in glial cells. Glial cells play a significant role in regulating overall nervous system health and disease conditions through a variety of functions unique to each glial subtype. However, detailed mechanisms by which tau toxicity manifests into disease states in specific glial subtypes are yet unknown. In this study, we utilized Drosophila melanogaster and its collaborative glial network to develop a glial tauopathy model that allows for subtype-specific tau overexpression. We investigated how tau expression, specifically in astrocyte-like glia (ALG) or cortical glia (CG), affects glial viability during development and hypothesized that human tau overexpression would yield glial cell subtype-specific toxicity with a more extensive impact in ALG than in CG. Results showed that while ALG-specific tau expression led to ALG cell count increase in young female flies, CG-specific tau expression led to extensive CG cell death in both sexes. Our study demonstrates that glial cell types respond differently to tau overexpression, highlighting the importance of evaluating each cell type individually in disease conditions.



tauopathy, tau, Drosophila melanogaster, glial cells, glial tauopathy, astrocyte-like glial cells, cortical glial cells, neurodegeneration