Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice

Masaki Ikeda, Mikio Shoji, Toshitaka Kawarai, Takeshi Kawarabayashi, Etsuro Matsubara, Tetsuro Murakami, Atsushi Sasaki, Yasushi Tomidokoro, Yasushi Ikarashi, Hisashi Kuribara, Koichi Ishiguro, Masato Hasegawa, Shu Hui Yen, M. Azhar Chishti, Yasuo Harigaya, Koji Abe, Koichi Okamoto, Peter St. George-Hyslop, David Westaway

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Abstract

Missense mutations of the tau gene cause autosomal dominant frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), an illness characterized by progressive personality changes, dementia, and parkinsonism. There is prominent frontotemporal lobe atrophy of the brain accompanied by abundant tau accumulation with neurofibrillary tangles and neuronal cell loss. Using a hamster prion protein gene expression vector, we generated several independent lines of transgenic (Tg) mice expressing the longest form of the human four-repeat tau with the R406W mutation associated with FTDP-17. The TgTauR406W 21807 line showed tau accumulation beginning in the hippocampus and amygdala at 6 months of age, which subsequently spread to the cortices and subcortical areas. The accumulated tau was phosphorylated, ubiquitinated, conformationally changed, argyrophilic, and sarcosyl-insoluble. Activation of GSK-3β and astrocytic induction of mouse tau were observed. Astrogliosis and microgliosis correlated with prominent tau accumulation. Electron microscopic examination revealed the presence of straight filaments. Behavioral tests showed motor disturbances and progressive acquired memory loss between 10 to 12 months of age. These findings suggested that TgTauR406W mice would be a useful model in the study of frontotemporal dementia and other tauopathies such as Alzheimer's disease (AD).

Original languageEnglish
Pages (from-to)521-531
Number of pages11
JournalAmerican Journal of Pathology
Volume166
Issue number2
Publication statusPublished - Feb 2005

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Frontotemporal Dementia
Cerebral Cortex
Transgenic Mice
Chromosomes, Human, Pair 17
Parkinsonian Disorders
Tauopathies
Glycogen Synthase Kinase 3
Neurofibrillary Tangles
Memory Disorders
Missense Mutation
Amygdala
Cricetinae
Atrophy
Personality
Dementia
Hippocampus
Alzheimer Disease
Electrons
Gene Expression
Mutation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Ikeda, M., Shoji, M., Kawarai, T., Kawarabayashi, T., Matsubara, E., Murakami, T., ... Westaway, D. (2005). Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice. American Journal of Pathology, 166(2), 521-531.

Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice. / Ikeda, Masaki; Shoji, Mikio; Kawarai, Toshitaka; Kawarabayashi, Takeshi; Matsubara, Etsuro; Murakami, Tetsuro; Sasaki, Atsushi; Tomidokoro, Yasushi; Ikarashi, Yasushi; Kuribara, Hisashi; Ishiguro, Koichi; Hasegawa, Masato; Yen, Shu Hui; Chishti, M. Azhar; Harigaya, Yasuo; Abe, Koji; Okamoto, Koichi; St. George-Hyslop, Peter; Westaway, David.

In: American Journal of Pathology, Vol. 166, No. 2, 02.2005, p. 521-531.

Research output: Contribution to journalArticle

Ikeda, M, Shoji, M, Kawarai, T, Kawarabayashi, T, Matsubara, E, Murakami, T, Sasaki, A, Tomidokoro, Y, Ikarashi, Y, Kuribara, H, Ishiguro, K, Hasegawa, M, Yen, SH, Chishti, MA, Harigaya, Y, Abe, K, Okamoto, K, St. George-Hyslop, P & Westaway, D 2005, 'Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice', American Journal of Pathology, vol. 166, no. 2, pp. 521-531.
Ikeda M, Shoji M, Kawarai T, Kawarabayashi T, Matsubara E, Murakami T et al. Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice. American Journal of Pathology. 2005 Feb;166(2):521-531.
Ikeda, Masaki ; Shoji, Mikio ; Kawarai, Toshitaka ; Kawarabayashi, Takeshi ; Matsubara, Etsuro ; Murakami, Tetsuro ; Sasaki, Atsushi ; Tomidokoro, Yasushi ; Ikarashi, Yasushi ; Kuribara, Hisashi ; Ishiguro, Koichi ; Hasegawa, Masato ; Yen, Shu Hui ; Chishti, M. Azhar ; Harigaya, Yasuo ; Abe, Koji ; Okamoto, Koichi ; St. George-Hyslop, Peter ; Westaway, David. / Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice. In: American Journal of Pathology. 2005 ; Vol. 166, No. 2. pp. 521-531.
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