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Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Wegmann, Susanne Maury, Eduardo A. Kirk, Molly J. Saqran, Lubna Roe, Allyson D. DeVos, Sarah L. Nicholls, Samantha B. Fan, Zhanyun Takeda, Shuko Cagsal-Getkin, Ozge William, Christopher M. P. Spires-Jones, Tara L. Pitstick, Rose Carlson, George L. Artist Pooler, Amy Melissa Hyman, Bradley T. |
| Copyright Year | 2015 |
| Abstract | In Alzheimer's disease and tauopathies, tau protein aggregates into neurofibrillary tangles that progressively spread to synaptically connected brain regions. A prion-like mechanism has been suggested: misfolded tau propagating through the brain seeds neurotoxic aggregation of soluble tau in recipient neurons. We use transgenic mice and viral tau expression to test the hypotheses that trans-synaptic tau propagation, aggregation, and toxicity rely on the presence of endogenous soluble tau. Surprisingly, mice expressing human P301Ltau in the entorhinal cortex showed equivalent tau propagation and accumulation in recipient neurons even in the absence of endogenous tau. We then tested whether the lack of endogenous tau protects against misfolded tau aggregation and toxicity, a second prion model paradigm for tau, using P301Ltau-overexpressing mice with severe tangle pathology and neurodegeneration. Crossed onto tau-null background, these mice had similar tangle numbers but were protected against neurotoxicity. Therefore, misfolded tau can propagate across neural systems without requisite templated misfolding, but the absence of endogenous tau markedly blunts toxicity. These results show that tau does not strictly classify as a prion protein. |
| Starting Page | 137 |
| Ending Page | 141 |
| Page Count | 5 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://www.research.ed.ac.uk/portal/files/21783771/EMBOJ_2015_92748_text.pdf |
| Alternate Webpage(s) | http://www.research.ed.ac.uk/portal/files/21783771/EMBOJ_2015_92748_text.pdf |
| Alternate Webpage(s) | http://embojnl.embopress.org/content/embojnl/34/24/3028.full.pdf |
| Alternate Webpage(s) | http://www.research.ed.ac.uk/portal/files/21783772/Figures_and_FiguresEV.pdf |
| Alternate Webpage(s) | http://embojnl.embopress.org/content/embojnl/34/24/3028.reviewer-comments.pdf |
| Alternate Webpage(s) | https://www.research.ed.ac.uk/portal/files/21783772/Figures_and_FiguresEV.pdf |
| PubMed reference number | 26538322v1 |
| Alternate Webpage(s) | https://doi.org/10.15252/embj.201592748 |
| DOI | 10.15252/embj.201592748 |
| Journal | The EMBO journal |
| Volume Number | 34 |
| Issue Number | 24 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adverse reaction to drug Alzheimer's Disease Cerebral cortex Nerve Degeneration Neurofibrillary degeneration (morphologic abnormality) Neurotoxicity Syndromes Null Value Plant seeds Prions Protein Aggregates Tau protein:PrThr:Pt:Body fld:Ord Tauopathies nervous system disorder |
| Content Type | Text |
| Resource Type | Article |
