{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T22:33:51Z","timestamp":1769121231790,"version":"3.49.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Mutations in the Integral membrane protein 2B (<jats:italic>ITM2B<\/jats:italic>) gene are linked to the development of familial British and Danish dementias, two relatively early\u2010onset dementia disorders known also to be associated with Tau neurofibrillary tangles (NFTs). However, to date, the involvement of ITM2B in limbic\u2010predominant age\u2010related TDP\u201043 encephalopathy neuropathologic changes (LATE\u2010NC) remains unclear. To address this question, we used brain samples from the University of Kentucky Alzheimer's Disease Research Center community\u2010based autopsy cohort. We investigated the patterns and co\u2010localizations of ITM2B immunohistochemistry in subiculum, CA1, CA2, CA3 and dentate gyrus of the hippocampus from brains with Alzheimer's disease neuropathologic changes (ADNC), LATE\u2010NC, and comorbid ADNC+LATE\u2010NC, as well as low\u2010pathology controls (<jats:italic>n<\/jats:italic>\u2009=\u20094 per disease state). There was frequent co\u2010localization between ITM2B protein and intracellular Tau pathology in ADNC; however, there was a far weaker rate of co\u2010localization between ITM2B and TDP\u201043 pathology. There also was, as previously described, an association between ITM2B immunostaining and neuritic\u2010appearing amyloid plaques. Additionally, co\u2010localization of intracellular ITM2B pathology with Thioflavin\u2010S in NFTs suggested a potential role for ITM2B in marking neurons undergoing transition from relatively healthy (early NFT\u2010bearing cells) to more severely affected (later NFT\u2010bearing) cellular disease states. This study indicates that ITM2B has a relatively specific pattern of involvement in Tau\u2010related neurodegeneration and in neuritic amyloid plaques, while implying minimal, if any, role for ITM2B in the synergistic relationship between Tau and TDP\u201043 pathologies.<\/jats:p>","DOI":"10.1111\/neup.70003","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T11:39:43Z","timestamp":1741693183000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessing Co\u2010Localization of <scp>ITM2B<\/scp> With Alzheimer's Disease and Limbic\u2010Predominant Age\u2010Related <scp>TDP<\/scp>\u201043 Encephalopathy Neuropathologic Changes"],"prefix":"10.1111","volume":"45","author":[{"given":"Ryan K.","family":"Shahidehpour","sequence":"first","affiliation":[{"name":"Spinal Cord and Brain Injury Research Center University of Kentucky  Lexington Kentucky USA"},{"name":"Department of Neuroscience University of Kentucky  Lexington Kentucky USA"},{"name":"Sanders\u2010Brown Center on Aging University of Kentucky  Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6161-1265","authenticated-orcid":false,"given":"Peter T.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Sanders\u2010Brown Center on Aging University of Kentucky  Lexington Kentucky USA"},{"name":"Department of Pathology and Laboratory Medicine, Division of Neuropathology University of Kentucky  Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukanya","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Sanders\u2010Brown Center on Aging University of Kentucky  Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong","family":"Yu","sequence":"additional","affiliation":[{"name":"Sanders\u2010Brown Center on Aging University of Kentucky  Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam D.","family":"Bachstetter","sequence":"additional","affiliation":[{"name":"Spinal Cord and Brain Injury Research Center University of Kentucky  Lexington Kentucky USA"},{"name":"Department of Neuroscience University of Kentucky  Lexington Kentucky USA"},{"name":"Sanders\u2010Brown Center on Aging University of Kentucky  Lexington Kentucky 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