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dc.contributor.authorPolanco, JC
dc.contributor.authorScicluna, BJ
dc.contributor.authorHill, AF
dc.contributor.authorGotz, J
dc.date.accessioned2020-12-22T03:31:29Z
dc.date.available2020-12-22T03:31:29Z
dc.date.issued2016-06-10
dc.identifierpii: S0021-9258(20)40890-7
dc.identifier.citationPolanco, J. C., Scicluna, B. J., Hill, A. F. & Gotz, J. (2016). Extracellular Vesicles Isolated from the Brains of rTg4510 Mice Seed Tau Protein Aggregation in a Threshold-dependent Manner. JOURNAL OF BIOLOGICAL CHEMISTRY, 291 (24), pp.12445-12466. https://doi.org/10.1074/jbc.M115.709485.
dc.identifier.issn0021-9258
dc.identifier.urihttp://hdl.handle.net/11343/257871
dc.description.abstractThe microtubule-associated protein tau has a critical role in Alzheimer disease and related tauopathies. There is accumulating evidence that tau aggregates spread and replicate in a prion-like manner, with the uptake of pathological tau seeds causing misfolding and aggregation of monomeric tau in recipient cells. Here we focused on small extracellular vesicles enriched for exosomes that were isolated from the brains of tau transgenic rTg4510 and control mice. We found that these extracellular vesicles contained tau, although the levels were significantly higher in transgenic mice that have a pronounced tau pathology. Tau in the vesicles was differentially phosphorylated, although to a lower degree than in the brain cells from which they were derived. Several phospho-epitopes (AT8, AT100, and AT180) thought to be critical for tau pathology were undetected in extracellular vesicles. Despite this, when assayed with FRET tau biosensor cells, extracellular vesicles derived from transgenic mice were capable of seeding tau aggregation in a threshold-dependent manner. We also observed that the dye used to label extracellular vesicle membranes was still present during nucleation and formation of tau inclusions, suggesting either a role for membranes in the seeding or in the process of degradation. Together, we clearly demonstrate that extracellular vesicles can transmit tau pathology. This indicates a role for extracellular vesicles in the transmission and spreading of tau pathology. The characteristics of tau in extracellular vesicles and the seeding threshold we identified may explain why tau pathology develops very slowly in neurodegenerative diseases such as Alzheimer disease.
dc.languageEnglish
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleExtracellular Vesicles Isolated from the Brains of rTg4510 Mice Seed Tau Protein Aggregation in a Threshold-dependent Manner
dc.typeJournal Article
dc.identifier.doi10.1074/jbc.M115.709485
melbourne.affiliation.departmentBiochemistry and Molecular Biology
melbourne.source.titleJournal of Biological Chemistry
melbourne.source.volume291
melbourne.source.issue24
melbourne.source.pages12445-12466
dc.rights.licenseCC BY
melbourne.elementsid1175009
melbourne.contributor.authorHill, Andrew
dc.identifier.eissn1083-351X
melbourne.accessrightsOpen Access


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