{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:46:14Z","timestamp":1789994774020,"version":"4.0.1"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,11,21]],"date-time":"2011-11-21T00:00:00Z","timestamp":1321833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:p>Primary lateral sclerosis (PLS) is clinically defined as a disorder selectively affecting the upper motor neuron (UMN) system. However, recently it has also been considered that PLS is heterogeneous in its clinical presentation. To elucidate the association of PLS, or disorders mimicking PLS, with 43\u2010kDa TAR DNA\u2010binding protein (TDP\u201043) abnormality, we examined two adult patients with motor neuron disease, which clinically was limited almost entirely to the UMN system, and was followed by progressive frontotemporal atrophy. In the present study, the distribution and severity, and biochemical profile of phosphorylated TDP\u201043 (pTDP\u201043) in the brains and spinal cords were examined immunohistochemically and biochemically. Pathologically, in both cases, frontotemporal lobar degeneration with ubiquitin inclusions (FTLD\u2010U) was evident, with the most severe degeneration in the motor cortex. An important feature in both cases was the presence of Bunina bodies and\/or ubiquitin inclusions, albeit very rarely, in the well preserved lower motor neurons. The amygdala and neostriatum were also affected. pTDP\u201043 immunohistochemistry revealed the presence of many positively stained neuronal cytoplamic inclusions (NCIs) and dystrophic neurites\/neuropil threads in the affected frontotemporal cortex and subcortical gray matter. By contrast, such pTDP\u201043 lesions, including NCIs, were observed in only a few lower motor neurons. pTDP\u201043 immunoblotting revealed that fragments of \u223c25\u2010kDa were present in the cortices, but not in the spinal cord in both cases. Genetically, neither of the patients had any mutation in the<jats:italic>TDP\u201043<\/jats:italic>gene. In conclusion, we consider that although PLS may be a clinically significant disease entity, at autopsy, the majority of such clinical cases would present as upper\u2010motor\u2010predominant amyotrophic lateral sclerosis with FTLD\u2010TDP.<\/jats:p>","DOI":"10.1111\/j.1440-1789.2011.01271.x","type":"journal-article","created":{"date-parts":[[2011,11,21]],"date-time":"2011-11-21T09:36:35Z","timestamp":1321868195000},"page":"373-384","source":"Crossref","is-referenced-by-count":61,"title":["Primary lateral sclerosis: Upper\u2010motor\u2010predominant amyotrophic lateral sclerosis with frontotemporal lobar degeneration \u2013 immunohistochemical and biochemical analyses of 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