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- W2616398857 abstract "Tau is a microtubule-associated protein exerting several physiological functions in neurons. In Alzheimer's disease (AD) misfolded tau accumulates intraneuronally and leads to axonal degeneration. However, tau has also been found in the extracellular medium. Recent studies indicated that extracellular tau uploaded from neurons causes synaptic dysfunction and contributes to tau pathology propagation. Here we report novel evidence that extracellular tau oligomers are abundantly and rapidly accumulated in astrocytes where they disrupt intracellular Ca2+ signaling and Ca2+ -dependent release of gliotransmitters, especially ATP. Consequently, synaptic vesicle release, the expression of pre- and postsynaptic proteins, and mEPSC frequency and amplitude were reduced in neighboring neurons. Notably, we found that tau uploading from astrocytes required the amyloid precursor protein, APP. Collectively, our findings suggests that astrocytes play a critical role in the synaptotoxic effects of tau via reduced gliotransmitter availability, and that astrocytes are major determinants of tau pathology in AD." @default.
- W2616398857 created "2017-05-26" @default.
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- W2616398857 date "2017-05-18" @default.
- W2616398857 modified "2023-10-03" @default.
- W2616398857 title "Reduced gliotransmitter release from astrocytes mediates tau-induced synaptic dysfunction in cultured hippocampal neurons" @default.
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- W2616398857 doi "https://doi.org/10.1002/glia.23163" @default.
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