RT Journal Article
SR Electronic
T1 The extracellular chaperone Clusterin enhances Tau aggregate seeding in a cellular model
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.16.452659
DO 10.1101/2021.07.16.452659
A1 Patricia Yuste-Checa
A1 Victoria A. Trinkaus
A1 Irene Riera-Tur
A1 Rahmi Imamoglu
A1 Theresa Schaller
A1 Huping Wang
A1 Irina Dudanova
A1 Mark S. Hipp
A1 Andreas Bracher
A1 F. Ulrich Hartl
YR 2021
UL http://biorxiv.org/content/early/2021/07/16/2021.07.16.452659.abstract
AB Spreading of aggregate pathology across brain regions acts as a driver of disease progression in Tau-related neurodegeneration, including Alzheimer’s disease (AD) and frontotemporal dementia. Aggregate seeds released from affected cells are internalized by naïve cells and induce the prion-like templating of soluble Tau into neurotoxic aggregates. Here we show in a cellular model system and in neurons that Clusterin, an abundant extracellular chaperone, strongly enhances Tau aggregate seeding. Upon interaction with Tau aggregates, Clusterin stabilizes highly potent, soluble seed species. Tau/Clusterin complexes enter recipient cells via endocytosis and compromise the endolysosomal compartment, allowing transfer to the cytosol where they propagate aggregation of endogenous Tau. Thus, upregulation of Clusterin, as observed in AD patients, may enhance Tau seeding and possibly accelerate the spreading of Tau pathology.Competing Interest StatementThe authors have declared no competing interest.