The extracellular chaperone Clusterin enhances Tau aggregate seeding in a cellular model

Variants of the extracellular chaperone Clusterin are associated with Alzheimer’s disease (AD) and Clusterin levels are elevated in AD patient brains. Here, the authors show that Clusterin binds to oligomeric Tau, which enhances the seeding capacity of Tau aggregates upon cellular uptake. They also...

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Autores principales: Patricia Yuste-Checa, Victoria A. Trinkaus, Irene Riera-Tur, Rahmi Imamoglu, Theresa F. Schaller, Huping Wang, Irina Dudanova, Mark S. Hipp, Andreas Bracher, F. Ulrich Hartl
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/6817e37ab6504c1fa561f4ad2a667e95
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Sumario:Variants of the extracellular chaperone Clusterin are associated with Alzheimer’s disease (AD) and Clusterin levels are elevated in AD patient brains. Here, the authors show that Clusterin binds to oligomeric Tau, which enhances the seeding capacity of Tau aggregates upon cellular uptake. They also demonstrate that Tau/Clusterin complexes enter cells via the endosomal pathway, resulting in damage to endolysosomes and entry into the cytosol, where they induce the aggregation of endogenous, soluble Tau.