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Article type: Research Article
Authors: Baker, Siân | Polanco, Juan Carlos | Götz, Jϋrgen*
Affiliations: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, St Lucia Campus (Brisbane), QLD, Australia
Correspondence: [*] Correspondence to: Jürgen Götz, Clem Jones Centre for Ageing Dementia Research (CJCADR), Queensland Brain Institute (QBI), The University of Queensland, St Lucia Campus (Brisbane), QLD 4072, Australia. Tel.: +61 7 3346 6329; Fax: +61 733466301; E-mail: [email protected].
Abstract: In Alzheimer’s disease, the distribution of neurofibrillary tangles, a histological hallmark comprised of phosphorylated forms of the protein tau, follows a distinct pattern through anatomically connected brain regions. The well-documented correlation between the severity of tau pathology and disease progression implies a prion-like seeding and spreading mechanism for tau. Experimentally, this has been addressed in transgenic mice by the injection of protein lysates isolated from brains of transgenic mice or patients with tauopathies, including AD, that were shown to behave like seeds, accelerating tau pathology and tangle formation in predisposed mice. More specifically, in vivo data suggest that brain lysates from mice harboring the P301S mutation of tau can seed protein aggregation when injected into the hippocampi of human wild-type tau transgenic ALZ17 mice. Here, we compared the seeding potential of lysates and extracellular vesicles enriched for exosomes (EVs) from wild-type and human P301L tau transgenic rTg4510 mouse brains. We show that transgenic EVs cause increased tau phosphorylation and soluble oligomer formation in a manner comparable to that of freely available proteins in brain lysates, a prerequisite for the formation of mature protein aggregates.
Keywords: Alzheimer’s disease, extracellular vesicles, phosphorylation, seeding, tau
DOI: 10.3233/JAD-160371
Journal: Journal of Alzheimer's Disease, vol. 54, no. 3, pp. 1207-1217, 2016
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