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Microglia-driven inflammation induces progressive tauopathies and synucleinopathies
Sang Hwan Lee1,2, Eun-Jin Bae1,2, Sung Jun Park1
1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Experimental & Molecular Medicine
|April 30, 2025
Summary
Microglia-driven inflammation can initiate and spread neurodegenerative diseases like Alzheimer's and Parkinson's. This inflammation alone triggers protein aggregates, neuropathology, and cognitive deficits, highlighting its early role.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Neurodegenerative diseases feature protein aggregates (tau, α-synuclein) and neuroinflammation.
- The role of microglia-driven inflammation in initiating and propagating these pathologies is unclear.
Purpose of the Study:
- To investigate if microglia-driven inflammation can independently trigger and spread neuropathology in neurodegenerative diseases.
Main Methods:
- Single-cell RNA sequencing of microglia exposed to α-synuclein or tau.
- Transplantation of activated microglia into naive mouse brains.
- Assessment of resulting tauopathy, synucleinopathy, gliosis, inflammation, and behavioral deficits.
Main Results:
- Microglia exposed to α-synuclein or tau showed distinct inflammatory responses.
- Transplanted microglia induced tauopathy, synucleinopathy, gliosis, and inflammation in recipient mice.
- Pathology and deficits spread beyond injection sites, affecting motor and cognitive functions.
Conclusions:
- Microglia-driven inflammation can initiate the full spectrum of neurodegenerative pathology.
- Inflammation-induced neuropathology can spread throughout the brain.
- Microglia-driven inflammation plays a critical, early role in neurodegeneration.
