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Recent studies have shown that pTDP-43 aggregates also occur in the skeletal muscles in a certain proportion of ALS patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The aim of this study was to clarify the distribution and incidence of pTDP-43 aggregates in the skeletal and cardiac muscles of patients with ALS, and also those of patients with neuromuscular diseases (NMDs) and non-NMDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and methods<\/jats:title>\n                    <jats:p>\n                      Five regions of muscle (tongue, cervical muscle, diaphragm, iliopsoas muscle and heart) were examined histologically and immunohistochemically in patients with ALS (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200930), NMDs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913) and non-NMDs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two types of pTDP-43 aggregates were distinguishable morphologically: dense filamentous and short linear inclusions. These inclusions were found in at least one of the five muscle regions in all 30 cases of ALS; skeletal muscles in 28 cases and myocardium in 12. pTDP-43 aggregates were also found in 9 of 13 patients with NMDs, including myositis, muscular dystrophy and mitochondrial myopathy, as well as in 3 of 7 patients with non-NMDs. In ALS, pTDP-43 aggregates were most frequent in the diaphragm (19 cases). The mean density of pTDP-43 aggregates in ALS was significantly higher than that in NMDs and non-NMDs. In contiguous sections stained with hematoxylin and eosin and anti-pTDP-43, muscle fibers with dense filamentous inclusions demonstrated single-fiber atrophy with vacuolar degeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The present findings indicate that pTDP-43 aggregates in skeletal and cardiac muscle are a myogenic pathological marker in multiple diseases including ALS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40478-019-0824-1","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T07:09:06Z","timestamp":1572246546000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Phosphorylated TDP-43 aggregates in skeletal and cardiac muscle are a marker of myogenic degeneration in amyotrophic lateral sclerosis and various conditions"],"prefix":"10.1186","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1903-1766","authenticated-orcid":false,"given":"Fumiaki","family":"Mori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Tada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Kon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Miki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunikazu","family":"Tanji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidekachi","family":"Kurotaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Tomiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Ishihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Onodera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiyoshi","family":"Kakita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Wakabayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,28]]},"reference":[{"key":"824_CR1","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s40478-014-0165-z","volume":"2","author":"S Al-Sarraj","year":"2014","unstructured":"Al-Sarraj S, King A, Cleveland M, Pradat PF, Corse A, Rothstein JD, Leigh PN, Abila B, Bates S, Wurthner J et al (2014) Mitochondrial abnormalities and low grade inflammation are present in the skeletal muscle of a minority of patients with amyotrophic lateral sclerosis; an observational myopathology study. 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