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Updated: Jul 1, 2026
09:22
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
Arc mediates intercellular tau transmission via extracellular vesicles
Mitali Tyagi1, Eric de Hoog1, Matthew Grega1
1Department of Neurobiology, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, USA.
Cell
|June 29, 2026
Summary
The neuronal gene Arc is crucial for releasing tau protein into extracellular vesicles (EVs), a key step in tau pathology spread. Eliminating Arc significantly reduces intercellular tau transmission in Alzheimer's disease models.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Tau pathology is a hallmark of neurodegenerative diseases like Alzheimer's disease (AD).
- Intercellular transmission of tau aggregates is a proposed mechanism for disease progression.
- The precise mechanisms driving tau release and cell-to-cell spread remain incompletely understood.
Purpose of the Study:
- To investigate the role of the neuronal gene Arc in the intercellular transmission of tau.
- To elucidate the molecular mechanisms by which tau is released from neurons.
Main Methods:
- Utilized transgenic rTg4510 mutant tau mice crossed with Arc knockout mice (rTgArc KO).
- Purified extracellular vesicles (EVs) from mouse and human brains.
- Assessed tau levels, seeding potential, and phosphorylation in EVs.
- Examined intracellular tau accumulation and cell toxicity in Arc KO mice.
Main Results:
- The neuronal gene Arc directly interacts with tau, facilitating its release via EVs.
- EVs from rTgArc KO mice showed significantly reduced tau content and seeding potential.
- Arc and tau were co-packaged within brain-derived EVs from both mice and humans.
- A positive correlation was observed between Arc levels and phosphorylated tau in EVs from human AD brains.
- Arc deficiency almost completely abolished intercellular tau transmission in mice, despite increased intracellular tau accumulation.
Conclusions:
- Arc is a critical mediator for the packaging and release of tau into EVs.
- EV-mediated tau release, regulated by Arc, plays a significant role in the cell-to-cell spread of tau pathology.
- Targeting the Arc-tau interaction in EVs could represent a novel therapeutic strategy for AD and other tauopathies.
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