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α-Synuclein in motor neuron disease: an immunohistologic study

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Abstract

α-Synuclein (ASN) has been implicated in neurodegenerative disorders characterized by Lewy body inclusions such as Parkinson’s disease and dementia with Lewy bodies. Lewy body-like inclusions have also been observed in spinal neurons of patients with amyotrophic lateral sclerosis (ALS) and reports suggest possible ASN abnormalities in ALS patients. We assessed ASN immunoreactivity in spinal and brain tissues of subjects who had died of progressive motor neuron disorders (MND). Clinical records of subjects with MND and a comparison group were reviewed to determine the diagnosis according to El-Escariol Criteria of ALS. Cervical, thoracic and lumbar cord sections were stained with an antibody to ASN. A blinded, semiquantitative review of sections from both groups included examination for evidence of spheroids, neuronal staining, cytoplasmic inclusions, anterior horn granules, white and gray matter glial staining, corticospinal tract axonal fiber and myelin changes. MND cases, including ALS and progressive muscular atrophy, displayed significantly increased ASN staining of spheroids (P≤0.001), and glial staining in gray and white matter (P≤0.05). Significant abnormal staining of corticospinal axon tract fibers and myelin was also observed (P≤0.05 and 0.01). Detection of possible ASN-positive neuronal inclusions did not differ between groups. Significant ASN abnormalities were observed in MND. These findings suggest a possible role for ASN in MND; however, the precise nature of this association is unclear.

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Acknowledgements

We would like to thank the laboratories of Robert Brown Jr. at the Cecil B. Day Laboratory for Neuromuscular Research, Boston, for SOD-1 screening and the Department of Neuropathology at the University of Washington for their cooperation in performing this study. We thank Lynne Greenup for her technical assistance. J.B.L. is funded with a Department of Veteran’s Affairs Merit Grant.

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Authors and Affiliations

  1. Mental Illness Research, Education, and Clinical Center, 116MIRECC, VA Puget Sound Healthcare System, 1660 S. Columbian Way, Seattle, WA, 98108, USA

    J. B. Leverenz

  2. Parkinson’s Disease Research, Education, and Clinical Center, VA Puget Sound Healthcare System, Seattle, Washington, USA

    J. B. Leverenz

  3. Geriatric Research, Education, and Clinical Center, VA Puget Sound Healthcare System, Seattle, Washington, USA

    T. D. Bird

  4. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA

    J. B. Leverenz

  5. Department of Medicine (Medical Genetics), University of Washington, Seattle, Washington, USA

    T. D. Bird

  6. Department of Neurology, University of Washington, Seattle, Washington, USA

    M. J. Doherty, T. D. Bird & J. B. Leverenz

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  1. M. J. Doherty
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Correspondence to J. B. Leverenz.

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Doherty, M.J., Bird, T.D. & Leverenz, J.B. α-Synuclein in motor neuron disease: an immunohistologic study. Acta Neuropathol 107, 169–175 (2004). https://doi.org/10.1007/s00401-003-0790-2

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  • DOI: https://doi.org/10.1007/s00401-003-0790-2

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