{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:15:35Z","timestamp":1788243335998,"version":"build-2803163510"},"reference-count":58,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["403694598"],"award-info":[{"award-number":["403694598"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["GR 1912\/13-1"],"award-info":[{"award-number":["GR 1912\/13-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["455978266"],"award-info":[{"award-number":["455978266"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["01KU2004"],"award-info":[{"award-number":["01KU2004"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["403694598"],"award-info":[{"award-number":["403694598"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["GR 1912\/13-1"],"award-info":[{"award-number":["GR 1912\/13-1"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["455978266"],"award-info":[{"award-number":["455978266"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["01KU2004"],"award-info":[{"award-number":["01KU2004"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although the common pathology of Alzheimer\u2019s disease (AD) and white matter hyperintensities (WMH) is disputed, the gene TREML2 has been implicated in both conditions: its whole-blood gene expression was associated with WMH volume and its missense variant rs3747742 with AD risk. We re-examined those associations within one comprehensive dataset of the general population, additionally searched for cross-relations and illuminated the role of the apolipoprotein E (APOE) \u03b54 status in the associations. For our linear regression and linear mixed effect models, we used 1949 participants from the Study of Health in Pomerania (Germany). AD was assessed using a continuous pre-symptomatic MRI-based score evaluating a participant\u2019s AD-related brain atrophy. In our study, increased whole-blood TREML2 gene expression was significantly associated with reduced WMH volume but not with the AD score. Conversely, rs3747742-C was significantly associated with a reduced AD score but not with WMH volume. The APOE status did not influence the associations. In sum, TREML2 robustly associated with WMH volume and AD-related brain atrophy on different molecular levels. Our results thus underpin TREML2\u2019s role in neurodegeneration, might point to its involvement in AD and WMH via different biological mechanisms, and highlight TREML2 as a worthwhile target for disentangling the two pathologies.<\/jats:p>","DOI":"10.3390\/ijms232213764","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T01:48:08Z","timestamp":1668044888000},"page":"13764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["TREML2 Gene Expression and Its Missense Variant rs3747742 Associate with White Matter Hyperintensity Volume and Alzheimer\u2019s Disease-Related Brain Atrophy in the General Population"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0158-8286","authenticated-orcid":false,"given":"Annemarie Luise","family":"K\u00fchn","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5087-5970","authenticated-orcid":false,"given":"Stefan","family":"Frenzel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8309-094X","authenticated-orcid":false,"given":"Alexander","family":"Teumer","sequence":"additional","affiliation":[{"name":"Institute for Community Medicine, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4383-5043","authenticated-orcid":false,"given":"Katharina","family":"Wittfeld","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Site Rostock\/Greifswald, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9067-8170","authenticated-orcid":false,"given":"Linda","family":"Garvert","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-0027","authenticated-orcid":false,"given":"Antoine","family":"Weihs","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6839-0605","authenticated-orcid":false,"given":"Georg","family":"Homuth","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2379-6286","authenticated-orcid":false,"given":"Holger","family":"Prokisch","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Technical University Munich, 81675 Munich, Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen-German Research Center for Environmental Health, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1884-5784","authenticated-orcid":false,"given":"Robin","family":"B\u00fclow","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Nauck","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475 Greifswald, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5689-3448","authenticated-orcid":false,"given":"Uwe","family":"V\u00f6lker","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"V\u00f6lzke","sequence":"additional","affiliation":[{"name":"Institute for Community Medicine, University Medicine Greifswald, 17475 Greifswald, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J\u00f6rgen","family":"Grabe","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Site Rostock\/Greifswald, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1757-7768","authenticated-orcid":false,"given":"Sandra","family":"Van der Auwera","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Site Rostock\/Greifswald, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"ref_1","unstructured":"Gauthier, S., Rosa-Neto, P., Morais, J., and Webster, C. 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