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- W2153299079 abstract "Tau is a predominantly axonal protein in neurons, where it plays a role in microtubule assembly and stabilisation. Mutations in the tau gene are associated with hereditary fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) and enhance the capacity for the protein to form aggregates in vitro. Aggregated tau proteins are also found in a variety of other neurodegenerative diseases including Alzheimer's disease (AD), in which they form the paired helical filaments that constitute the neurofibrillary lesions. To model tau aggregation in vivo, a transgenic mouse model (line 66) expressing full-length tau carrying a double mutation (P301S/G335D) under the control of the murine Thy1-promoter was generated on an NMRI background. Brain sections were stained using Bielschowsky silver stain and Thioflavin S and immunohistochemically with mAb 7/51. Homozygous and heterozygous mice together with wild-type NMRI were assessed in a number of behavioural tasks: the SHIRPA screen, open field, rotarod, balance beam, catwalk and grip strength meter. The expression of the mutant tau was associated with a prominent and progressive motor impairment in line 66 mice. At 4 months, homozygous mice show decreased speed and locomotor activity in the open field and an impaired performance on the rotarod compared to wild-type mice. The SHIRPA protocol also revealed a number of changes in motor-related parameters in homozygous mice. At 7 months, SHIRPA analysis in heterozygous animals showed deterioration in some motor parameters relative to 4-month old animals. By contrast, 7-month old homozygous mice displayed a palsy-like shaking, which was paralleled by a stronger impairment in grip strength, ability in rotarod and balance beam tasks and severe alterations in gait analysed with the catwalk. Histologically, tau-positive tangles were observed that were also positive for silver and Thioflavin S staining. Line 66 tau-transgenic mice exhibit a strong motor-phenotype, reminiscent of certain characteristics of parkinsonism and serve as a model for motor defects associated with certain tauopathies." @default.
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- W2153299079 date "2009-07-01" @default.
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- W2153299079 title "P4-039: Overexpression of mutant tau in mice leads to tau aggregation and deterioration of motor skills" @default.
- W2153299079 doi "https://doi.org/10.1016/j.jalz.2009.04.909" @default.
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