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Concomitant accumulation of α-synuclein and TDP-43 in a patient with corticobasal degeneration

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Abstract

Pathological changes in corticobasal degeneration (CBD) consist of abnormal deposition of the microtubule-associated protein tau. However, the simultaneous accumulation of different misfolded proteins in the brain can be observed in many neurodegenerative diseases with significantly longer disease durations. We encountered a patient with CBD who survived for an extremely long period (18 years) after the diagnosis. We performed an autopsy to elucidate the effect of the longer survival on the pathology of CBD. We observed abnormal aggregation of trans-activating response region DNA-binding protein of 43 kDa (TDP-43) and α-synuclein, as well as phosphorylated tau, in neurons of broader regions of the brain, beyond the amygdala and other limbic areas. We found that phosphorylated tau, α-synuclein, and TDP-43 partially co-existed in the same cellular aggregates. The triple pathologic changes might be related to the longer survival of the patient compared with the typical clinical course of patients with CBD. Further investigations are required to support the hypothesis that tauopathy, synucleinopathy, and TDP-43 proteinopathy might share common pathogenic mechanisms in terms of cross-seeding of the pathologic proteins.

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Acknowledgments

We would like to thank Ms. Mika Oka and the members of Department of Neurology, Kumamoto University Hospital for technical help with autopsy analyses and clinical data collection. This work was supported by a Grant-in-Aid for Scientific Research, the Ministry of Education, Culture, Sports, Science and Technology of Japan, and Grants-in-Aid from the Amyloidosis Research Committee, the Ministry of Health, Labour and Welfare of Japan.

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical standard

This study has been approved by the appropriate ethics committee and has therefore been performed in the accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. The spouse of the patient gave informed consent instead of the patient.

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Authors and Affiliations

  1. Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan

    Satoshi Yamashita, Taro Yamashita, Nozomu Tawara, Masayoshi Tasaki, Kensuke Kawakami, Teruyuki Hirano, Yasushi Maeda & Yukio Ando

  2. Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan

    Naomi Sakashita, Yoshihiro Komohara, Yukio Fujiwara, Masashi Kamikawa, Takenobu Nakagawa & Motohiro Takeya

  3. Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan

    Naomi Sakashita

  4. Department of Internal Medicine, 3rd Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, 879-5593, Japan

    Teruyuki Hirano

  5. Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan

    Masato Hasegawa

Authors
  1. Satoshi Yamashita
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  2. Naomi Sakashita
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  3. Taro Yamashita
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Corresponding author

Correspondence to Satoshi Yamashita.

Additional information

S. Yamashita, N. Sakashita and T. Yamashita authors contributed equally to the manuscript.

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Yamashita, S., Sakashita, N., Yamashita, T. et al. Concomitant accumulation of α-synuclein and TDP-43 in a patient with corticobasal degeneration. J Neurol 261, 2209–2217 (2014). https://doi.org/10.1007/s00415-014-7491-8

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  • DOI: https://doi.org/10.1007/s00415-014-7491-8

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