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  • Title: Degeneration of spinocerebellar neurons in amyotrophic lateral sclerosis.
    Author: Williams C, Kozlowski MA, Hinton DR, Miller CA.
    Journal: Ann Neurol; 1990 Mar; 27(3):215-25. PubMed ID: 2327732.
    Abstract:
    The selective involvement of spinocerebellar neurons in sporadic amyotrophic lateral sclerosis was investigated using two monoclonal antibodies that have neuronal subset specificity in human spinal cord. In normal control subjects, monoclonal antibody 6A2 showed specificity for neurons of the dorsal nucleus of Clarke, the cells of origin of the dorsal spinocerebellar tract. Immunoreactive neurons were also observed in locations corresponding to the central cervical nucleus and spinal border region, containing neurons of the cervicospinocerebellar and ventral spinocerebellar tracts, respectively. The latter two neuronal subsets are indistinguishable from surrounding neurons when conventional histological stains are used. Antigen 6A2 was distributed on surfaces of neuronal somas and proximal neurites and extended into the extracellular space. A second antibody, monoclonal antibody 44.1, labeled the cytoplasm of neuronal somas and neurites, including all monoclonal antibody 6A2-reactive cells and alpha motoneurons. In spinal cords of all 5 patients with amyotrophic lateral sclerosis, monoclonal antibody 6A2 reactivity in the majority of spinocerebellar neurons was absent or localized to the somal cytoplasm, which still stained with monoclonal antibody 44.1. In more severely involved tissues, there was loss of some spinocerebellar neurons and a corresponding loss of monoclonal antibody 44.1 reactivity. These findings confirm involvement of the spinal cord components of the spinocerebellar system at all levels in sporadic amyotrophic lateral sclerosis and suggest that some surface molecules are modified during the degenerative process.
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