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Identification and Quantification of Oligodendrocyte Precursor Cells in Multiple System Atrophy, Progressive Supranuclear Palsy and Parkinson's Disease

Authors

  • Zeshan Ahmed,

    1. Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
    2. Queen Square Brain Bank, UCL Institute of Neurology, London, UK
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  • Yasmine T. Asi,

    1. Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
    2. Queen Square Brain Bank, UCL Institute of Neurology, London, UK
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  • Andrew J. Lees,

    1. Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
    2. Queen Square Brain Bank, UCL Institute of Neurology, London, UK
    3. Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK
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  • Tamas Revesz,

    1. Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
    2. Queen Square Brain Bank, UCL Institute of Neurology, London, UK
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  • Janice L. Holton

    Corresponding author
    1. Queen Square Brain Bank, UCL Institute of Neurology, London, UK
    2. Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK
    • Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
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Corresponding author:

Janice L. Holton, FRCPath, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK (E-mail: janice.holton@ucl.ac.uk)

Abstract

Multiple system atrophy is a neurodegenerative disorder characterized pathologically by abnormal accumulations of α-synuclein in the cytoplasm of oligodendrocytes, which are termed glial cytoplasmic inclusions (GCIs). Oligodendrocytes are responsible for myelinating axons and providing neurotrophic support, but in MSA, myelin loss, axonal loss and gliosis are consistent features suggesting that GCIs play a central role in disease pathogenesis. Oligodendroglial, myelin and axonal degeneration are also features of multiple sclerosis (MS) in which recent studies have highlighted the robust remyelination capacity of the central nervous system (CNS). The cells responsible for remyelination are called oligodendroglial precursor cells (OPCs). In this study, we investigated the role of OPCs in the pathogenesis of MSA and progressive supranuclear palsy (PSP), a neurodegenerative disease in which neuropathological changes include oligodendroglial inclusions composed of microtubule-associated protein tau. Despite the lability of OPC-specific antigens, we successfully identified OPCs and demonstrated that tau and α-synuclein do not accumulate in OPCs. We also showed that the density of OPCs was increased in a white matter region of the MSA brain, which is also severely affected by GCIs and myelin degeneration. These findings raise the possibility that OPCs could be available to repair disease-associated damage in MSA, consistent with their biological function.

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