Arc mediates intercellular tau transmission via extracellular vesicles.

ABSTRACT: Intracellular neurofibrillary tangles that consist of misfolded tau protein¹ cause neurodegeneration in Alzheimer's disease (AD) and frontotemporal dementia (FTD). Tau pathology spreads cell-to-cell² but the exact mechanisms of tau release and intercellular transmission remain poorly defined. Tau is released from neurons as free protein or in extracellular vesicles (EVs)^3-5 but the role of these different release mechanisms in intercellular tau transmission is unclear. Here, we show that the neuronal gene Arc is critical for packaging tau into EVs. Brain EVs purified from human tau (hTau) transgenic rTg4510 mice (rTg^WT) contain high levels of hTau that are capable of seeding tau pathology. In contrast, EVs purified from rTg^WT crossed w

SUBMITTER: Tyagi M 

PROVIDER: S-EPMC11526995 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature