{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:29:22Z","timestamp":1790393362370,"version":"4.1.0"},"reference-count":49,"publisher":"BMJ","issue":"2","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"accepted":{"date-parts":[[2019,10,7]]},"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Since the first report of<jats:italic>CHCHD10<\/jats:italic>gene mutations in amyotrophiclateral sclerosis (ALS)\/frontotemporaldementia (FTD) patients, genetic variation in<jats:italic>CHCHD10<\/jats:italic>has been inconsistently linked to disease. A pathological assessment of the CHCHD10 protein in patient neuronal tissue also remains to be reported. We sought to characterise the genetic and pathological contribution of CHCHD10 to ALS\/FTD in Australia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole-exome and whole-genome sequencing data from 81 familial and 635 sporadic ALS, and 108 sporadic FTD cases, were assessed for genetic variation in<jats:italic>CHCHD10<\/jats:italic>. CHCHD10 protein expression was characterised by immunohistochemistry, immunofluorescence and western blotting in control, ALS and\/or FTD postmortem tissues and further in a transgenic mouse model of TAR DNA-binding protein 43 (TDP-43) pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No causal, novel or disease-associated variants in<jats:italic>CHCHD10<\/jats:italic>were identified in Australian ALS and\/or FTD patients. In human brain and spinal cord tissues, CHCHD10 was specifically expressed in neurons. A significant decrease in CHCHD10 protein level was observed in ALS patient spinal cord and FTD patient frontal cortex. In a TDP-43 mouse model with a regulatable nuclear localisation signal (rNLS TDP-43 mouse), CHCHD10 protein levels were unaltered at disease onset and early in disease, but were significantly decreased in cortex in mid-stage disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Genetic variation in<jats:italic>CHCHD10<\/jats:italic>is not a common cause of ALS\/FTD in Australia. However, we showed that in humans, CHCHD10 may play a neuron-specific role and a loss of CHCHD10 function may be linked to ALS and\/or FTD. Our data from the rNLS TDP-43 transgenic mice suggest that a decrease in CHCHD10 levels is a late event in aberrant TDP-43-induced ALS\/FTD pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2019-321790","type":"journal-article","created":{"date-parts":[[2019,11,5]],"date-time":"2019-11-05T22:25:18Z","timestamp":1572992718000},"page":"162-171","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Genetic and immunopathological analysis of CHCHD10 in Australian amyotrophic lateral sclerosis and frontotemporal dementia and transgenic TDP-43 mice"],"prefix":"10.1136","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8200-3525","authenticated-orcid":false,"given":"Emily P","family":"McCann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0814-0118","authenticated-orcid":false,"given":"Jennifer 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