STRUCTURAL AND IMMUNOCYTOCHEMICAL FEATURES OF OLIVOPONTOCEREBELLAR ATROPHY CAUSED BY THE SPINOCEREBELLAR ATAXIA TYPE-1 (SCA-1) MUTATION DEFINE A UNIQUE PHENOTYPE

Neuropathological investigations performed on autopsied brain and spin al cords from Ii patients showed that spinocerebellar ataxia type 1 (S CA-1) can be distinguished from autosomal dominant spinocerebellar ata xia linked to SCA-2 and -3 loci on chromosomes 12 and 14, spinopontine , and the multisystem atrophies. The major diagnostic criteria were: a bsence of significant pars compacta nigral and locus cocruleus lesions , severe degeneration of olivocerebellar and dentatorubral pathways, e xtensive loss of Purkinje cells with partial sparing of flocculonodula r lobes, severe atrophy of specific cranial nerve nuclei, mostly the t hird and 12th, extensive loss of motor neurons in anterior horns and C larke's columns, and lack of oligodendroglial or neuronal cytoplasmic cytoskeletal inclusions. None of the brains displayed any significant immunoreactivity for the amyloid precursor protein or beta-amyloid pep tide throughout the cortex. In conclusion, the type and neuroanatomica l distribution of structural lesions were similarly reproduced in all probands at the end stage of SCA-1, to the point that they appeared to constitute a unique phenotype.