Affiliations: [a] Department of Neuroscience, University of Torino, Torino, Italy
| [b] Neuroscience Institute of Cavalieri Ottolenghi Foundation (NICO), University of Torino, Torino, Italy
| [c] Department of Internal Medicine and Medical Specialties (DIMI), Unit of Geriatric Medicine, University of Genova, Genova, Italy
| [d] IRCS San Martino-IST, University of Genova, Genova, Italy
| [e] Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, USA
Correspondence:
[*]
Correspondence to: Prof. Massimo Tabaton, Department of Internal Medicine and Medical Specialities (DIMI) Viale Benedetto XV, 6,16132, Genova, Italy. Tel./Fax: +390103537064; E-mail: [email protected].
Abstract: 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.
Keywords: Alzheimer’s disease, hTau mice, paired helical filaments, tau protein
