{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:48:40Z","timestamp":1790434120068,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,12,19]],"date-time":"2011-12-19T00:00:00Z","timestamp":1324252800000},"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":[[2012,10]]},"abstract":"<jats:p>The transactive response DNA binding protein (TDP\u201043) proteinopathies describe a clinico\u2010pathological spectrum of multi\u2010system neurodegeneration that spans motor neuron disease\/amyotrophic lateral sclerosis (MND\/ALS) and frontotemporal lobar degeneration (FTLD). We have identified four male patients who presented with the clinical features of a pure MND\/ALS phenotype (without dementia) but who had distinctive cortical and cerebellar pathology that was different from other TDP\u201043 proteinopathies. All patients initially presented with weakness of limbs and respiratory muscles and had a family history of MND\/ALS. None had clinically identified cognitive decline or dementia during life and they died between 11 and 32 months after symptom onset. Neuropathological investigation revealed lower motor neuron involvement with TDP\u201043\u2010positive inclusions typical of MND\/ALS. In contrast, the cerebral pathology was atypical, with abundant star\u2010shaped p62\u2010immunoreactive neuronal cytoplasmic inclusions in the cerebral cortex, basal ganglia and hippocampus, while TDP\u201043\u2010positive inclusions were sparse. This pattern was also seen in the cerebellum where p62\u2010positive, TDP\u201043\u2010negative inclusions were frequent in granular cells. Western blots of cortical lysates, in contrast to those of sporadic MND\/ALS and FTLD\u2010TDP, showed high p62 levels and low TDP\u201043 levels with no high molecular weight smearing. MND\/ALS\u2010associated <jats:italic>SOD1, FUS<\/jats:italic> and <jats:italic>TARDBP<\/jats:italic> gene mutations were excluded; however, further investigations revealed that all four of the cases did show a repeat expansion of <jats:italic>C9orf72<\/jats:italic>, the recently reported cause of chromosome 9\u2010linked MND\/ALS and FTLD. We conclude that these chromosome 9\u2010linked MND\/ALS cases represent a pathological sub\u2010group with abundant p62 pathology in the cerebral cortex, hippocampus and cerebellum but with no significant associated cognitive decline.<\/jats:p>","DOI":"10.1111\/j.1440-1789.2011.01286.x","type":"journal-article","created":{"date-parts":[[2011,12,20]],"date-time":"2011-12-20T02:24:19Z","timestamp":1324347859000},"page":"505-514","source":"Crossref","is-referenced-by-count":102,"title":["An MND\/ALS phenotype associated with <i>C9orf72<\/i> repeat expansion: Abundant p62\u2010positive, TDP\u201043\u2010negative inclusions in cerebral cortex, hippocampus and cerebellum but without associated cognitive decline"],"prefix":"10.1111","volume":"32","author":[{"given":"Claire","family":"Troakes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satomi","family":"Maekawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lokesh","family":"Wijesekera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Rogelj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Sikl\u00f3s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Newhouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Vance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibor","family":"Hortob\u00e1gyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksey","family":"Shatunov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammar","family":"Al\u2010Chalabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Leigh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safa","family":"Al\u2010Sarraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,12,19]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1134108"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.2741\/2727"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2778"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq111"},{"key":"e_1_2_6_6_2","volume-title":"Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders","author":"Kato S","year":"2003"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/362059a0"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410430319"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/425287"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1742"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1154584"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1165942"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08971"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0813-3"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl030"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-010-5815-x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70197-6"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.09.010"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.09.011"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1967.00470210008002"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2009.01029.x"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.070182"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0612-2"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-008-0460-5"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31816a1da2"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2010.01171.x"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2008.00147.x"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.1978.tb01174.x"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.3109\/10520296009114754"},{"key":"e_1_2_6_30_2","volume-title":"Histological Techniques for Electron Microscopy","author":"Pease DC","year":"1960"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.17.1.208"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0237-2"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2009.204081"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0911-2"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64369-6"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702824200"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70071-1"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21392"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05016"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0545-9"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21948"}],"container-title":["Neuropathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1440-1789.2011.01286.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1440-1789.2011.01286.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T15:15:15Z","timestamp":1698678915000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1440-1789.2011.01286.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,19]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["10.1111\/j.1440-1789.2011.01286.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1440-1789.2011.01286.x","archive":["Portico"],"relation":{},"ISSN":["0919-6544","1440-1789"],"issn-type":[{"value":"0919-6544","type":"print"},{"value":"1440-1789","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12,19]]}}}