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Deposition of Phosphorylated α-Synuclein in the rTg4510 Mouse Model of Tauopathy
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- Yuta Takaichi
- Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
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- Yasuhisa Ano
- Research Laboratories for Health Science & Food Technologies and the Central Laboratories for Key Technologies, Kirin Company Ltd., Kanagawa, Japan
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- James K Chambers
- Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
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- Kazuyuki Uchida
- Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
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- Akihiko Takashima
- Department of Life Science, Faculty of Science, Gakushuin University, Tokyo, Japan
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- Hiroyuki Nakayama
- Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
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Description
The accumulation of specific phosphorylated protein aggregates in the brain is a hallmark of severe neurodegenerative disorders. Specifically, hyperphosphorylated tau (hp-tau) accumulates in Alzheimer disease, frontotemporal dementia with Parkinsonism linked to chromosome 17, and progressive supranuclear palsy; furthermore, phosphorylated α-synuclein (p-αSyn) accumulates in Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. Moreover, codeposition of different pathological protein aggregates is common in the brains of individuals with neurodegenerative diseases. In the present report, we describe the detection of p-αSyn aggregates in the brain of rTg4510 mice that overexpress human P301L mutant tau. Immunohistochemistry showed that hp-tau and p-αSyn aggregates were found within the same neuronal cells in rTg4510 mice and increased with age. Moreover, semiquantitative analysis revealed a significant regional correlation between hp-tau and p-αSyn accumulation. These results indicate that endogenous mouse αSyn protein is phosphorylated and accumulates with hp-tau aggregation in neurons and suggest that the overexpression of human P301L mutant tau may enhance endogenous αSyn phosphorylation and aggregation via a similar hyperphosphorylation mechanism in vivo. This synergic effect between tau and αSyn accumulation may exacerbate the pathology of several neurodegenerative disorders that show a cooccurrence of hp-tau and p-αSyn aggregation.
Journal
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- Journal of Neuropathology & Experimental Neurology
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Journal of Neuropathology & Experimental Neurology 77 (10), 920-928, 2018-07-18
Oxford University Press (OUP)
