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Herein, we examined the detailed pathology of the primary motor area and pyramidal tracts in the central nervous system in four autopsy cases of FTLD\u2010TDP type C, all of which were diagnosed by neuropathological, biochemical, and genomic analyses. Three patients showed right dominant atrophy of the frontal and temporal lobes, while the other patient showed left dominant atrophy. All four patients showed motor symptoms, and two patients had episodes of repeated aspiration. In the primary motor area, phosphorylated TDP\u201043 (p\u2010TDP\u201043) or annexin A11\u2010immunoreactive long dystrophic neurites were observed in all cases, and neuronophagia of the Betz cells was frequently observed in two of four cases. In the lower motor system, p\u2010TDP\u201043 or annexin A11\u2010positive dystrophic neurites were detected in the anterior horn of the spinal cord. Immuno\u2010electron microscopy of the insoluble fraction extracted from all cases showed p\u2010TDP\u201043 or annexin A11\u2010labelled filaments. In FTLD\u2010TDP type C, neurodegeneration with TDP and annexin A11 pathology was observed mainly in the upper motor neurons of both patients with right\u2010 and left predominant temporal atrophy and a short disease duration. Furthermore, a combination of TDP\u201043 and annexin A11 pathology was visible in the lower motor neurons, albeit less frequently. In summary, we reported the TDP\u201043 and annexin A11\u2010associated involvement of anterior horn cells of the spinal cord for the first time. The degeneration of the motor system could contribute to dysphagia and aspiration pneumonia at the late stage of FTLD\u2010TDP type C. Little or no TDP pathology was found in the corticospinal tract, unlike in FTLD\u2010TDP type B, suggesting the occurrence of secondary degeneration in FTLD\u2010TDP type C.<\/jats:p>","DOI":"10.1111\/neup.13026","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T21:48:53Z","timestamp":1736891333000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Motor involvement in frontotemporal lobar degeneration with <scp>TAR DNA<\/scp>\u2010binding protein of <scp>43\u2009kDa<\/scp> type C"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3142-073X","authenticated-orcid":false,"given":"Rika","family":"Yamashita","sequence":"first","affiliation":[{"name":"Department of Neurology Osaka University Graduate School of Medicine  Osaka 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