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Corticobasal degeneration with olivopontocerebellar atrophy and TDP-43 pathology: an unusual clinicopathologic variant of CBD

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Abstract

Corticobasal degeneration (CBD) is a disorder affecting cognition and movement due to a progressive neurodegeneration associated with distinctive neuropathologic features, including abnormal phosphorylated tau protein in neurons and glia in cortex, basal ganglia, diencephalon, and brainstem, as well as ballooned neurons and astrocytic plaques. We identified three cases of CBD with olivopontocerebellar atrophy (CBD-OPCA) that did not have α-synuclein-positive glial cytoplasmic inclusions of multiple system atrophy (MSA). Two patients had clinical features suggestive of progressive supranuclear palsy (PSP), and the third case had cerebellar ataxia thought to be due to idiopathic OPCA. Neuropathologic features of CBD-OPCA are compared to typical CBD, as well as MSA and PSP. CBD-OPCA and MSA had marked neuronal loss in pontine nuclei, inferior olivary nucleus, and Purkinje cell layer. Neuronal loss and grumose degeneration in the cerebellar dentate nucleus were comparable in CBD-OPCA and PSP. Image analysis of tau pathology showed greater infratentorial tau burden, especially in pontine base, in CBD-OPCA compared with typical CBD. In addition, CBD-OPCA had TDP-43 immunoreactive neuronal and glial cytoplasmic inclusions and threads throughout the basal ganglia and in olivopontocerebellar system. CBD-OPCA met neuropathologic research diagnostic criteria for CBD and shared tau biochemical characteristics with typical CBD. These results suggest that CBD-OPCA is a distinct clinicopathologic variant of CBD with olivopontocerebellar TDP-43 pathology.

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Acknowledgments

The authors thank Virginia Philips, Linda Rousseau, and Monica Castanedes-Casey for their expert technical assistance, Dr. Peter Davies at The Feinstein Institute for Medical Research, Manhasset, NY, for the gifts of CP13 and PHF-1 antibodies, and Dr. Rosa Rademakers for assisting with the genetic studies. Two of the CBD-OPCA cases and most of the PSP and CBD cases in this study were submitted to the CurePSP brain bank at Mayo Clinic in Jacksonville, FL; one was originally submitted to Department of Pathology and Laboratory Medicine diagnostic evaluation at Mayo Clinic in Rochester, MN. The studies would not have been possible without generous donations of family members and their contributions in this endeavor are greatly appreciated. This study was supported by NIH grants: P50-AG016574, P50–NS072187, CurePSP | Society for Progressive Supranuclear Palsy, The Robert E. Jacoby Professorship for Alzheimer’s Research, and Mayo Foundation for Education and Research.

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Author notes

  1. Kenichi Oshima

    Present address: Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan

  2. Makio Takahashi

    Present address: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan

  3. Zeshan Ahmed

    Present address: Reta Lila Weston Institute of Neurological Studies, University College London, London, UK

Authors and Affiliations

  1. Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA

    Naomi Kouri, Kenichi Oshima, Makio Takahashi, Melissa E. Murray, Zeshan Ahmed, Shu-Hui C. Yen & Dennis W. Dickson

  2. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Joseph E. Parisi

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  1. Naomi Kouri
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Corresponding author

Correspondence to Dennis W. Dickson.

Additional information

N. Kouri and K. Oshima contributed equally to this study.

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Kouri, N., Oshima, K., Takahashi, M. et al. Corticobasal degeneration with olivopontocerebellar atrophy and TDP-43 pathology: an unusual clinicopathologic variant of CBD. Acta Neuropathol 125, 741–752 (2013). https://doi.org/10.1007/s00401-013-1087-8

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  • DOI: https://doi.org/10.1007/s00401-013-1087-8

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