{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:58:20Z","timestamp":1791248300378,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T00:00:00Z","timestamp":1430352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UK NIHR Biomedical Research Centre for Ageing and Age-Related Disease"},{"name":"MRC"},{"name":"Wellcome Trust"},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"crossref","award":["G0400074"],"award-info":[{"award-number":["G0400074"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"crossref","award":["G1100540"],"award-info":[{"award-number":["G1100540"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Newcastle NIHR Biomedical Research Centre in Ageing and Age Related Diseases"},{"DOI":"10.13039\/501100000320","name":"Alzheimer's Society","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000320","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Alzheimer's Research UK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2015,8]]},"abstract":"\n Aims<\/jats:title>\n \n Frontotemporal lobar degeneration (\n FTLD<\/jats:styled-content>\n ) and motor neurone disease are linked by the possession of a hexanucleotide repeat expansion in\n \n C9ORF72<\/jats:italic>\n <\/jats:styled-content>\n , and both show neuronal cytoplasmic inclusions within cerebellar and hippocampal neurones which are\n TDP<\/jats:styled-content>\n \u201043 negative but immunoreactive for p62 and dipeptide repeat proteins (\n DPR<\/jats:styled-content>\n ), these being generated by a non\u2010\n ATG RAN<\/jats:styled-content>\n translation of the expanded region of the gene.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Twenty\u2010two cases of\n FTLD<\/jats:styled-content>\n from\n N<\/jats:styled-content>\n ewcastle were analysed for an expansion in\n \n C9ORF72<\/jats:italic>\n <\/jats:styled-content>\n by repeat primed\n PCR<\/jats:styled-content>\n and\n S<\/jats:styled-content>\n outhern blot. Detailed case note analysis was performed, and blinded retrospective clinical impressions were achieved by review of clinical histories. Sections from all major brain regions were immunostained for\n TDP<\/jats:styled-content>\n \u201043, p62 and\n DPR<\/jats:styled-content>\n . The extent of\n TDP<\/jats:styled-content>\n \u201043 and\n DPR<\/jats:styled-content>\n pathology in expansion bearers was compared with that in 13 other previously identified cases from the\n M<\/jats:styled-content>\n anchester\n B<\/jats:styled-content>\n rain\n B<\/jats:styled-content>\n ank with established disease.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Three Newcastle patients bearing an expansion in\n \n C9ORF72<\/jats:italic>\n <\/jats:styled-content>\n were identified. These three patients died prematurely, two from bronchopneumonia within 10 months and 3 years of onset, and one from myocardial infarction 3 years after onset. In all three,\n DPR<\/jats:styled-content>\n were plentiful throughout all cerebral cortical regions, hippocampus and cerebellum, but\n TDP<\/jats:styled-content>\n \u201043 pathological changes were sparse. The severity of\n DPR<\/jats:styled-content>\n pathological changes in these three patients was similar to that in the\n M<\/jats:styled-content>\n anchester series, although the extent of\n TDP<\/jats:styled-content>\n \u201043 pathology was significantly less.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Widespread accumulation of\n DPR<\/jats:styled-content>\n within nerve cells may occur much earlier than that of\n TDP<\/jats:styled-content>\n \u201043 in patients with\n FTLD<\/jats:styled-content>\n bearing expansion in\n \n C9ORF72<\/jats:italic>\n <\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/nan.12178","type":"journal-article","created":{"date-parts":[[2014,9,3]],"date-time":"2014-09-03T05:51:10Z","timestamp":1409723470000},"page":"601-612","source":"Crossref","is-referenced-by-count":69,"title":["Accumulation of dipeptide repeat proteins predates that of\n TDP<\/scp>\n \u201043 in frontotemporal lobar degeneration associated with hexanucleotide repeat expansions in\n \n C9ORF72<\/i>\n <\/scp>\n gene"],"prefix":"10.1111","volume":"41","author":[{"given":"Atik","family":"Baborie","sequence":"first","affiliation":[{"name":"Department of Neuropathology Walton Centre for Neurology and Neurosurgery Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Newcastle University Medical School Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Jaros","sequence":"additional","affiliation":[{"name":"Neuropathology\/Cellular Pathology Royal Victoria Infirmary Newcastle upon Tyne UK"},{"name":"Institute for Ageing and Health Newcastle University, Campus for Ageing and Vitality Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Perry","sequence":"additional","affiliation":[{"name":"Neuropathology\/Cellular Pathology Royal Victoria Infirmary Newcastle upon Tyne UK"},{"name":"Institute for Ageing and Health Newcastle University, Campus for Ageing and Vitality Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian G.","family":"McKeith","sequence":"additional","affiliation":[{"name":"Institute for Ageing and Health Newcastle University, Campus for Ageing and Vitality Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Burn","sequence":"additional","affiliation":[{"name":"Institute for Ageing and Health Newcastle University, Campus for Ageing and Vitality Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Masuda\u2010Suzukake","sequence":"additional","affiliation":[{"name":"Department of Neuropathology and Cell Biology Tokyo Metropolitan Institute of Medical Science Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Neuropathology and Cell Biology Tokyo Metropolitan Institute of Medical Science Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Rollinson","sequence":"additional","affiliation":[{"name":"Institute of Brain, Behaviour and Mental Health University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Pickering\u2010Brown","sequence":"additional","affiliation":[{"name":"Institute of Brain, Behaviour and Mental Health University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Institute of Brain, Behaviour and Mental Health University of Manchester, Salford Royal Hospital Salford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne S.","family":"Davidson","sequence":"additional","affiliation":[{"name":"Institute of Brain, Behaviour and Mental Health University of Manchester, Salford Royal Hospital Salford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M. 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