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Glial cytoplasmic inclusions in neurologically normal elderly: prodromal multiple system atrophy?

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Abstract

In this study, we used immunohistochemistry to screen for α-synuclein pathology in the brains of 241 individuals without clinical evidence of neurologic disease, and discovered 36 cases (15%) with incidental Lewy bodies (LBs) and one case, a 96-year-old woman (0.4%), with inclusions similar to those seen in multiple system atrophy (MSA), a non-familial neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia and autonomic dysfunction and α-synuclein immunoreactive glial cytoplasmic inclusions (GCI). In a routine hospital autopsy series of 125 brains, we detected GCI in a neurologically normal 82-year-old man (0.8%). Both cases showed widespread GCI in the central nervous system, as well as a few neuronal cytoplasmic inclusions, but no neuronal loss or gliosis in vulnerable brain regions, including the substantia nigra, putamen, inferior olive and pontine base. Applying a recently proposed grading scale for MSA, the two cases showed pathology far below that detected in patients with clinically overt MSA, suggesting the possibility that these two individuals had preclinical MSA. The prevalence of clinically overt MSA is estimated to be about 4 per 100,000 persons (0.004%), which is far less than the frequency of GCI in this series (0.4–0.8%). Further studies are needed to determine if GCI in neurologically normal elderly represents prodromal MSA or a rare non-progressive age-related α-synucleinopathy.

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Acknowledgments

Supported by NIH grants P50-AG16574, P50-NS40256 and R01-AG15866, Pacific Alzheimer Research Foundation (PARF) grant C06-01.

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Authors and Affiliations

  1. Departments of Pathology (Neuropathology) and Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL, 32224, USA

    Hiroshige Fujishiro, Tae-Beom Ahn, Anthony DelleDonne & Dennis W. Dickson

  2. Department of Neurology, Mayo Clinic, Rochester, MN, USA

    Roberta Frigerio, Keith A. Josephs & J. Eric Ahlskog

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

    Joseph E. Parisi

Authors
  1. Hiroshige Fujishiro
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  2. Tae-Beom Ahn
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  3. Roberta Frigerio
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  4. Anthony DelleDonne
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  5. Keith A. Josephs
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  6. Joseph E. Parisi
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  7. J. Eric Ahlskog
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  8. Dennis W. Dickson
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Correspondence to Dennis W. Dickson.

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Fujishiro, H., Ahn, TB., Frigerio, R. et al. Glial cytoplasmic inclusions in neurologically normal elderly: prodromal multiple system atrophy?. Acta Neuropathol 116, 269–275 (2008). https://doi.org/10.1007/s00401-008-0398-7

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  • DOI: https://doi.org/10.1007/s00401-008-0398-7

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