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P4‐040: Plaque‐associated dystrophic neurite pathology in three transgenic mice lines carrying human APP FAD mutations are indicative of structural injury to axons and identical to preclinical Alzheimer's disease
Author(s) -
Vickers James C.,
Mitev Stan,
Woodhouse Adele,
Adlard Paul A.,
Dickson Tracey C.
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.910
Subject(s) - neurite , neurofilament , presenilin , genetically modified mouse , pathology , axon , alzheimer's disease , biology , axoplasmic transport , transgene , neuroscience , immunohistochemistry , medicine , disease , biochemistry , in vitro , gene
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. Conclusions: 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.