Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer’s disease or corticobasal degeneration brains
[eng] Filamentous tau pathologies are the hallmark lesions of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and corticobasal degeneration (CBD). These diseases show cell type-specific and topographically distinct tau inclusions. Growing evidence supports templated transmis...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/106429 |
| Acceso en línea: | https://hdl.handle.net/2445/106429 http://hdl.handle.net/10803/399674 |
| Access Level: | acceso abierto |
| Palabra clave: | Malaltia d'Alzheimer Ratolins transgènics Degeneració Alzheimer's disease Transgenic mice Degeneration |
| Sumario: | [eng] Filamentous tau pathologies are the hallmark lesions of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and corticobasal degeneration (CBD). These diseases show cell type-specific and topographically distinct tau inclusions. Growing evidence supports templated transmission of tauopathies through functionally interconnected neuroanatomical pathways suggesting that different self-propagating strains of pathological tau could account for the diverse manifestations of neurodegenerative tauopathies. In the study, the rapid induction of tau pathology and the distinct cell type-specific spread of pathological tau following intracerebral injections of CBD or AD brain extracts enriched in pathological tau in human mutant P301S tau transgenic (Tg) mice (line PS19) is analysed. At 1 mo post-injection of extracts obtained from brains with CBD pathology (CBD-Tau), tau inclusions developed predominantly in oligodendrocytes of the fimbria and white matter near the injection sites with infrequent intraneuronal tau aggregates. In contrast, injections of enriched tau extracts from brains with AD pathology (AD-Tau) in young PS19 mice induced tau pathology predominantly in neuronal perikarya with little or no oligodendrocyte involvement 1 mo post-injection. With longer post-injection survival intervals of up to 6 mo, CBD-Tau and AD-Tau induced tau pathology spread to different brain regions distant from the injection sites while maintaining the cell type specific pattern noted above. In conclusion, these experiments provide evidence for the prion-like hypothesis of disease spread and suggest that the tau pathology formed in vivo is dependent on the tau pathology in the preparation indicating that there are post-translational modifications or strains of tau protein that are responsible for the variation between diseases. |
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