{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:40:36Z","timestamp":1772160036285,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T00:00:00Z","timestamp":1722384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_PC_17164"],"award-info":[{"award-number":["MC_PC_17164"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000320","name":"Alzheimer's Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000320","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Transmembrane and coiled\u2010coil 2 (TMCC2) is a human orthologue of the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    gene\n                    <jats:italic>dementin<\/jats:italic>\n                    , mutant alleles of which cause neurodegeneration with features of Alzheimer's disease (AD). TMCC2 and Dementin further have an evolutionarily conserved interaction with the amyloid protein precursor (APP), a protein central to AD pathogenesis. To investigate if human TMCC2 might also participate in mechanisms of neurodegeneration, we examined TMCC2 expression in late onset AD human brain and age\u2010matched controls, familial AD cases bearing a mutation in APP Val717, and Down syndrome AD. Consistent with previous observations of complex formation between TMCC2 and APP in the rat brain, the dual immunocytochemistry of control human temporal cortex showed highly similar distributions of TMCC2 and APP. In late onset AD cases stratified by APOE genotype, TMCC2 immunoreactivity was associated with dense core senile plaques and adjacent neuronal dystrophies, but not with A\u03b2 surrounding the core, diffuse A\u03b2 plaques or tauopathy. In Down syndrome AD, we observed in addition TMCC2\u2010immunoreactive and methoxy\u2010X04\u2010positive pathological features that were morphologically distinct from those seen in the late onset and familial AD cases, suggesting enhanced pathological alteration of TMCC2 in Down syndrome AD. At the protein level, western blots of human brain extracts revealed that human brain\u2010derived TMCC2 exists as at least three isoforms, the relative abundance of which varied between the temporal gyrus and cerebellum and was influenced by APOE and\/or dementia status. Our findings thus implicate human TMCC2 in AD via its interactions with APP, its association with dense core plaques, as well as its alteration in Down syndrome AD.\n                  <\/jats:p>","DOI":"10.1111\/bpa.13290","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T20:59:26Z","timestamp":1722459566000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transmembrane and coiled\u2010coil 2 associates with Alzheimer's disease pathology in the human brain"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9357-7022","authenticated-orcid":false,"given":"Paul C. R.","family":"Hopkins","sequence":"first","affiliation":[{"name":"Centre for Developmental Neurobiology King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1790-7376","authenticated-orcid":false,"given":"Claire","family":"Troakes","sequence":"additional","affiliation":[{"name":"London Neurodegenerative Diseases Brain Bank Institute of Psychiatry, Psychology and Neuroscience, King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7974-2589","authenticated-orcid":false,"given":"Andrew","family":"King","sequence":"additional","affiliation":[{"name":"London Neurodegenerative Diseases Brain Bank Institute of Psychiatry, Psychology and Neuroscience, King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3114-7537","authenticated-orcid":false,"given":"Guy","family":"Tear","sequence":"additional","affiliation":[{"name":"Centre for Developmental Neurobiology King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,31]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-102115"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055810"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2011.52"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2003.12.023"},{"key":"e_1_2_11_6_1","first-page":"503","article-title":"Chemical and immunological heterogeneity of fibrillar amyloid in plaques of Alzheimer's disease and Down's syndrome brains revealed by confocal 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