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SCA2 is accompanied by motor neuron degeneration as occurs in amyotrophic lateral sclerosis (ALS). We investigated the distribution patterns of ataxin-2 and transactivation-responsive DNA-binding protein 43 (TDP-43), a major disease-related protein in ALS, in the CNS of 3 SCA2 patients. Phosphorylated TDP-43 (pTDP-43)-positive lesions were widely distributed throughout the CNS and generally overlapped with 1C2 (expanded polyglutamine)-immunoreactive lesions. This distribution pattern is different from the pattern in limbic-predominant age-related TDP-43 encephalopathy. In SCA2, double immunostaining of TDP-43 and 1C2 in motor neurons revealed 3 staining patterns: cytoplasmic 1C2 and nuclear TDP-43, nucleocytoplasmic 1C2 and nuclear TDP-43, and nuclear 1C2 and cytoplasmic TDP-43, which reflect the early, active, and final stages of pathological change, respectively. The translocation of TDP-43 from the nucleus to the cytoplasm along with the translocation of 1C2 in the opposite direction indicates that nuclear accumulation of the disease-specific protein ataxin-2 affects the intracellular dynamics of TDP-43. Such a close interrelationship between mutant ataxin-2 and TDP-43 in the cell might account for the similarity of their distribution in the CNS of patients with SCA2.<\/jats:p>","DOI":"10.1093\/jnen\/nlac032","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T15:51:50Z","timestamp":1651765910000},"page":"535-544","source":"Crossref","is-referenced-by-count":6,"title":["Parallel Appearance of Polyglutamine and Transactivation-Responsive DNA-Binding Protein 43 and Their Complementary Subcellular Localization in Brains of Patients With Spinocerebellar Ataxia Type 2"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7424-4302","authenticated-orcid":false,"given":"Shigeru","family":"Koyano","sequence":"first","affiliation":[{"name":"Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine , Yokohama, Kanagawa, Japan"},{"name":"Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science , Tokyo, Japan"},{"name":"Department of Neurology, Yokohama Minami Kyosai Hospital , Yokohama, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saburo","family":"Yagishita","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine , Yokohama, Kanagawa, Japan"},{"name":"Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikiko","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine , Yokohama, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Doi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine , Yokohama, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiki","family":"Uchihara","sequence":"additional","affiliation":[{"name":"Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science , Tokyo, Japan"},{"name":"Neurology Clinic with Neuromorphomics Laboratory, Nitobe-Memorial Nakano General Hospital , Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiaki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine , Yokohama, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"key":"2024032523454935500_nlac032-B1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/ng1196-269","article-title":"Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2","volume":"14","author":"Pulst","year":"1996","journal-title":"Nat Genet"},{"key":"2024032523454935500_nlac032-B2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/ng1196-277","article-title":"Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT","volume":"14","author":"Sanpei","year":"1996","journal-title":"Nat Genet"},{"key":"2024032523454935500_nlac032-B3","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/ng1196-285","article-title":"Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG\/glutamine repeats","volume":"14","author":"Imbert","year":"1996","journal-title":"Nat Genet"},{"key":"2024032523454935500_nlac032-B4","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s12311-008-0019-y","article-title":"Spinocerebellar ataxia 2 (SCA2)","volume":"7","author":"Lastres-Becker","year":"2008","journal-title":"Cerebellum"},{"key":"2024032523454935500_nlac032-B5","first-page":"255","article-title":"Autosomal dominant spinocerebellar degenerations. 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