Cortical Neuronal and Glial Pathology in TgTauP301L Transgenic Mice
| Autor: | Erwan Paitel, Toshitaka Kawarai, Katsunori Iwasaki, Atsushi Sasaki, Koji Abe, Jing Yang, Mikio Shoji, Patrick Horne, Yasuo Harigaya, George A. Carlson, Peter St George-Hyslop, Christopher Janus, Mitsuo Takahashi, Nobuaki Egashira, M. Azhar Chishti, Takeshi Kawarabayashi, David Westaway, Amanda Hanna, Amie L. Phinney, Koichi Ishiguro, Etsuro Matsubara, Kenichi Mishima, Masaki Ikeda, Tetsuro Murakami, Michihiro Fujiwara, Catherine Bergeron |
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| Rok vydání: | 2006 |
| Předmět: |
Pathology
medicine.medical_specialty Parkinsonism Tau protein Biology medicine.disease Pathology and Forensic Medicine Progressive supranuclear palsy medicine.anatomical_structure Gliosis Cerebral cortex mental disorders medicine biology.protein Dementia Corticobasal degeneration medicine.symptom Frontotemporal dementia |
| Zdroj: | The American Journal of Pathology. 169:1365-1375 |
| ISSN: | 0002-9440 |
| Popis: | Recapitulation of tau pathologies in an animal model has been a long-standing goal in neurodegenerative disease research. We generated transgenic (TgTau P301L ) mice expressing a frontotemporal dementia with parkinsonism linked to chromosome 17 (FTPD-17) mutation within the longest form of tau (2N, 4R). TgTau P301L mice developed florid pathology including neuronal pretangles, numerous Gallyas-Braak-positive neurofibrillary tangles, and glial fibrillary tangles in the frontotemporal areas of the cerebrum, in the brainstem, and to a lesser extent in the spinal cord. These features were accompanied by gliosis, neuronal loss, and cerebral atrophy. Accumulated tau was hyperphosphorylated, conformationally changed, ubiquitinated, and sarkosyl-insoluble, with electron microscopy demonstrating wavy filaments. Aged TgTau P301L mice exhibited impairment in hippocampally dependent and independent behavioral paradigms, with impairments closely related to the presence of tau pathologies and levels of insoluble tau protein. We conclude that TgTau P301L mice recreate the substantial phenotypic variation and spectrum of pathologies seen in FTDP-17 patients. Identification of genetic and/or environmental factors modifying the tau phenotype in these mice may shed light on factors modulating human tauopathies. These transgenic mice may aid therapeutic development for FTDP-17 and other diseases featuring accumulations of four-repeat tau, such as Alzheimer's disease, corticobasal degeneration, and progressive supranuclear palsy. |
| Databáze: | OpenAIRE |
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