Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 59, Issue 2, Pages 743-751Publisher
IOS PRESS
DOI: 10.3233/JAD-170298
Keywords
Alzheimer's disease; hTau mice; paired helical filaments; tau protein
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Funding
- Italian Ministry of Health [RF 2010-2305605]
- Regione Piemonte
- University of Torino
- Compagnia di San Paolo [2013-0929]
- Veronesi Foundation
- NIH-NIA grant [R01AG049 402]
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The mechanism of tau toxicity is still unclear. Here we report that recombinant tau oligomers and monomers, intraventricularly injected in mice with a pure human tau background, foster tau pathology through different mechanisms. Oligomeric forms of tau alter the conformation of tau in a paired helical filament-like manner. This effect occurs without tau hyperphosphorylation as well as activation of specific kinases, suggesting that oligomers of tau induce tau assembly through a nucleation effect. Monomers, in turn, induce neurodegeneration through a calpain-mediated tau cleavage that leads to accumulation of a 17 kDa neurotoxic peptide and induction of apoptotic cell death.
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