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α-Synuclein pathology in the neostriatum in Parkinson’s disease

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Abstract

We immunohistochemically examined the neostriatum from 25 patients with symptomatic and presymptomatic Parkinson’s disease (PD) with various degrees of Lewy body pathology, using anti-phosphorylated α-synuclein (αS) antibody. These patients were classified according to the PD staging proposed by Braak et al. (Neurobiol Aging 24:197–211, 2003): stage II (αS pathology confined to the medulla oblongata and pontine tegmentum), stage III (αS pathology confined to the brainstem), stage IV (limbic stage), and stages V and VI (neocortical stage). αS immunohistochemistry revealed neuronal and glial cytoplasmic inclusions and neuritic changes in the neostriatum. αS inclusions were found in the medium-sized neurons (GABAergic neurons that project to the globus pallidus) and large neurons (cholinergic interneurons); the former began to appear at stage III and the latter was noted at stages V and VI. Neuritic changes and glial inclusions also began to appear at stage III. The numbers of neuronal and glial inclusions, and the extent of neuritic changes, correlated with the PD stage (P < 0.001). These findings suggest that intrinsic neostriatal neurons degenerate through αS aggregation during PD progression.

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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (to K.W.), a grant from the Research Committee on Neurodegenerative Diseases, Ministry of Health, Labor and Welfare, Japan (to H.T.), and the Karoji Memorial Fund for Medical Research (to K.T.). The authors wish to express their gratitude to M. Nakata for her technical assistance.

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Authors and Affiliations

  1. Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan

    Fumiaki Mori, Kunikazu Tanji, Haixin Zhang & Koichi Wakabayashi

  2. Department of Pathological Neuroscience, Center for Bioresource-based Researches, Brain Research Institute, University of Niigata, Niigata, Japan

    Akiyoshi Kakita

  3. Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan

    Hitoshi Takahashi

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  1. Fumiaki Mori
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Correspondence to Fumiaki Mori.

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Mori, F., Tanji, K., Zhang, H. et al. α-Synuclein pathology in the neostriatum in Parkinson’s disease. Acta Neuropathol 115, 453–459 (2008). https://doi.org/10.1007/s00401-007-0316-4

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  • DOI: https://doi.org/10.1007/s00401-007-0316-4

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