Extracellular vesicles containing P301L mutant tau accelerate pathological tau phosphorylation and oligomer formation but do not seed mature neurofibrillary tangles in ALZ17 mice

Baker, Sian, Polanco, Juan Carlos and Gotz, Juergen (2016) Extracellular vesicles containing P301L mutant tau accelerate pathological tau phosphorylation and oligomer formation but do not seed mature neurofibrillary tangles in ALZ17 mice. Journal of Alzheimer's Disease, 54 3: 1207-1217. doi:10.3233/JAD-160371


Author Baker, Sian
Polanco, Juan Carlos
Gotz, Juergen
Title Extracellular vesicles containing P301L mutant tau accelerate pathological tau phosphorylation and oligomer formation but do not seed mature neurofibrillary tangles in ALZ17 mice
Journal name Journal of Alzheimer's Disease   Check publisher's open access policy
ISSN 1875-8908
1387-2877
Publication date 2016-01-01
Year available 2016
Sub-type Article (original research)
DOI 10.3233/JAD-160371
Open Access Status Not yet assessed
Volume 54
Issue 3
Start page 1207
End page 1217
Total pages 11
Place of publication Amsterdam, Netherlands
Publisher I O S Press
Language eng
Subject 3203 Clinical Psychology
2717 Geriatrics and Gerontology
2738 Psychiatry and Mental health
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.
Keyword Alzheimer's disease
Extracellular vesicles
Phosphorylation
Seeding
Tau
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID DP13300101932
GNT1037746
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Centre for Ageing Dementia Research Publications
 
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