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Amyotrophic lateral sclerosis with dementia: an autopsy case showing many Bunina bodies, tau-positive neuronal and astrocytic plaque-like pathologies, and pallido-nigral degeneration

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Abstract

We report the case of a 54-year-old woman with mental retardation who developed frontotemporal dementia and amyotrophic lateral sclerosis (ALS) in the presenium. She presented with dementia at age 48, and motor neuron signs developed at age 53. She had no family history of dementia or ALS. Postmortem examination disclosed histopathological features of ALS, including pyramidal tract degeneration, mild loss of motor neurons, and many Bunina bodies immunoreactive for cystatin C, but not ubiquitin-positive inclusions. Unusual features of this case included severe neuronal loss in the substantia nigra and medial globus pallidus. The subthalamic nucleus, limbic system, and cerebral cortex were well preserved. In addition, neurofibrillary tangles (NFTs) were found in the frontal, temporal, insular, and cingulate cortices, nucleus basalis of Meynert, and locus coeruleus, and to a lesser degree, in the dentate nucleus, cerebellum, hippocampus, and amygdala. No ballooned neurons, tufted astrocytes, or astrocytic plaques were found. Tau immunostaining demonstrated many pretangles rather than NFTs and glial lesions resembling astrocytic plaques in the frontal and temporal cortices. This glial tau pathology predominantly developed in the middle to deep layers in the primary motor cortex, and was frequently associated with the walls of blood vessels. NFTs were immunolabeled with 3-repeat and 4-repeat specific antibodies against tau, respectively. Although the pathophysiological relationship between tau pathology and the selective involvement of motor neurons, substantia nigra, and globus pallidus was unclear, we considered that it might be more than coincidental.

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Acknowledgments

We would like to thank Ms. C. Haga, Ms. H. Kondo, Mr. Y. Shoda, Ms. E. Matsui, and Ms. K. Suzuki (Tokyo Institute of Psychiatry) and Ms. M. Onbe (Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry) for their excellent technical assistance and Mr. A. Sasaki for help with the production of the manuscript. This work was supported by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology (14570957) and a research grant from the Zikei Institute of Psychiatry.

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Authors and Affiliations

  1. Department of Neuropathology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo, 156-8585, Japan

    Osamu Yokota, Kuniaki Tsuchiya, Tetsuaki Arai & Haruhiko Akiyama

  2. Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

    Osamu Yokota, Takeshi Ishihara, Hideki Ishizu & Shigetoshi Kuroda

  3. Department of Laboratory Medicine and Pathology, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan

    Kuniaki Tsuchiya

  4. Department of Neurology, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan

    Kuniaki Tsuchiya

  5. Department of Psychiatry, National Hospital Organization, Shimofusa Psychiatric Center, Chiba, Japan

    Tatsurou Oda

  6. Reta Lila Weston Institute of Neurological Studies, University College London, London, UK

    Rohan de Silva & Andrew J. Lees

  7. Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan

    Toshiki Uchihara

  8. Department of Laboratory Medicine, Zikei Institute of Psychiatry, Okayama, Japan

    Hideki Ishizu

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  1. Osamu Yokota
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  2. Kuniaki Tsuchiya
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  11. Haruhiko Akiyama
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Correspondence to Osamu Yokota.

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Yokota, O., Tsuchiya, K., Oda, T. et al. Amyotrophic lateral sclerosis with dementia: an autopsy case showing many Bunina bodies, tau-positive neuronal and astrocytic plaque-like pathologies, and pallido-nigral degeneration. Acta Neuropathol 112, 633–645 (2006). https://doi.org/10.1007/s00401-006-0141-1

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  • DOI: https://doi.org/10.1007/s00401-006-0141-1

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