{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:11:55Z","timestamp":1789135915746,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,8]]},"group-title":"Neuroscience","reference-count":21,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Alzheimer disease neuropathologic change (ADNC) does not fully explain clinical severity, suggesting important contributions from coexisting pathologies. We examined major co-pathologies in a multicenter autopsy cohort, focusing on hippocampal\/medial temporal sclerosis (HS\/MTL sclerosis), clinical severity, regional TDP-43 topography, clinical status near death, and gross hippocampal atrophy. We analyzed longitudinal clinical and neuropathology data from the National Alzheimer\u2019s Coordinating Center autopsy cohort. Form-specific definitions harmonized AD pathology, major co-pathologies, HS\/MTL sclerosis, and regional TDP-43 findings across neuropathology versions 8\u201310. HS\/MTL sclerosis was present in 13.0% of assessed AD cases and was associated with greater CDR\u00ae Dementia Staging Instrument sum-of-boxes severity in non-AD (odds ratio [OR], 4.93; 95% confidence interval [CI], 3.66\u20136.63) and AD strata (OR, 2.56; 95% CI, 2.15\u20133.04). In version 10, HS\/MTL sclerosis was associated with higher regional TDP-43 topography (OR, 6.54; 95% CI, 3.88\u201311.02) and greater gross hippocampal atrophy (OR, 6.43; 95% CI, 4.97\u20138.32). Among AD cases assessed within 2 years of death, HS-negative participants had greater odds of non-dementia status than HS-positive participants (OR, 5.81; 95% CI, 2.80\u201312.06). HS\/MTL sclerosis marked greater clinical severity in both AD and non-AD strata and co-occurred with regional TDP-43 involvement and hippocampal atrophy. Its absence identified a subset with intermediate\/high AD pathology but no dementia near death. Clinical severity therefore cannot be inferred from ADNC alone.<\/jats:p>","DOI":"10.64898\/2026.09.03.749099","type":"posted-content","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:30:23Z","timestamp":1788874223000},"source":"Crossref","is-referenced-by-count":0,"title":["Hippocampal\/medial temporal sclerosis is associated with clinical severity, regional TDP-43, and hippocampal atrophy in Alzheimer disease"],"prefix":"10.64898","author":[{"given":"Preeti","family":"Sharma","sequence":"first","affiliation":[{"name":"Centre for Brain Research, Indian Institute of Science, Bengaluru 560012, India"},{"name":"Manipal Academy of Higher Education, Manipal 576104, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajath","family":"Devappa","sequence":"additional","affiliation":[{"name":"Centre for Brain Research, Indian Institute of Science, Bengaluru 560012, India"},{"name":"Manipal Academy of Higher Education, Manipal 576104, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivaprakasam R.","family":"Saroja","sequence":"additional","affiliation":[{"name":"Centre for Brain Research, Indian Institute of Science, Bengaluru 560012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091106550709000_2026.09.03.749099v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"2026091106550709000_2026.09.03.749099v1.2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0910-3"},{"key":"2026091106550709000_2026.09.03.749099v1.3","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000271090.28148.24"},{"key":"2026091106550709000_2026.09.03.749099v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25380"},{"key":"2026091106550709000_2026.09.03.749099v1.5","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e318142774e"},{"key":"2026091106550709000_2026.09.03.749099v1.6","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nly049"},{"key":"2026091106550709000_2026.09.03.749099v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.09.015"},{"key":"2026091106550709000_2026.09.03.749099v1.8","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21154"},{"key":"2026091106550709000_2026.09.03.749099v1.9","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz099"},{"key":"2026091106550709000_2026.09.03.749099v1.10","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24388"},{"key":"2026091106550709000_2026.09.03.749099v1.11","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200001"},{"key":"2026091106550709000_2026.09.03.749099v1.12","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14262"},{"key":"2026091106550709000_2026.09.03.749099v1.13","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaf158"},{"key":"2026091106550709000_2026.09.03.749099v1.14","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010454"},{"key":"2026091106550709000_2026.09.03.749099v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.11.015"},{"key":"2026091106550709000_2026.09.03.749099v1.16","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180942"},{"key":"2026091106550709000_2026.09.03.749099v1.17","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-019-0479-y"},{"key":"2026091106550709000_2026.09.03.749099v1.18","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200832"},{"key":"2026091106550709000_2026.09.03.749099v1.19","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-019-0733-3"},{"key":"2026091106550709000_2026.09.03.749099v1.20","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-022-02524-2"},{"key":"2026091106550709000_2026.09.03.749099v1.21","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-024-02728-8"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.03.749099","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:55:12Z","timestamp":1789134912000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.03.749099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":21,"URL":"https:\/\/doi.org\/10.64898\/2026.09.03.749099","relation":{},"subject":[],"published":{"date-parts":[[2026,9,8]]},"subtype":"preprint"}}