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Patterns of neuronal degeneration in the motor cortex of amyotrophic lateral sclerosis patients

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Summary

We examined patterns of neuronal degeneration in the motor cortex of amyotrophic lateral selerosis (ALS) patients using traditional cell stains and several histochemical markers including neurofilament, parvalbumin, NADPH-diaphorase, ubiquitin, Alz-50 and tau. Three grades of ALS (mild, moderate, severe) were defined based on the extent of Betz cell depletion. Non-phosphorylated neurofilament immunoreactive cortical pyramidal neurons and non-pyramidal parvalbumin local circuit neurons were significantly depleted in all grades of ALS. In contrast, NADPH-diaphorase neurons and Alz-50-positive neurons were quantitatively preserved despite reduced NADPH-diaphorase cellular staining and dendritic pruning. The density of ubiquitin-positive structures in the middle and deep layers of the motor cortex was increased in all cases. Axonal tau immunoreactivity was not altered. These histochemical results suggest that cortical degeneration in ALS is distinctive from other neurodegenerative diseases affecting cerebral cortex. Unlike Huntington's disease, both pyramidal and local cortical neurons are affected in ALS; unlike Alzheimer's disease, alteration of the neuronal cytoskeleton is not prominent. The unique pattern of neuronal degeneration found in ALS motor cortex is consistent with non-N-methyl-Dxxx-aspartate glutamate receptor-mediated cytotoxicity.

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Authors and Affiliations

  1. Neurology Service, Massachusetts General Hospital, 02114, Boston, MA, USA

    Kuninobu Nihei & Neil W. Kowall

  2. Department of Neuropathology, Massachusetts General Hospital, 02114, Boston, MA, USA

    Ann C. McKee & Neil W. Kowall

  3. The Third Department of Internal Medicine, Yamagata University, 990-23, Yamagata, Japan

    Kuninobu Nihei

  4. Department of Neurology, Boston University School of Medicine, Boston, USA

    Neil W. Kowall

  5. Department of Pathology, Boston University School of Medicine, Boston, USA

    Neil W. Kowall

  6. Geriatric Research Education Clinical Center, Bedford VA Medical Center, 200 Springs Road, 01730, Bedford, MA, USA

    Neil W. Kowall

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  1. Kuninobu Nihei
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  2. Ann C. McKee
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Supported in part by a Muscular Dystrophy Association Research Development grant

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Nihei, K., McKee, A.C. & Kowall, N.W. Patterns of neuronal degeneration in the motor cortex of amyotrophic lateral sclerosis patients. Acta Neuropathol 86, 55–64 (1993). https://doi.org/10.1007/BF00454899

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