{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:19:02Z","timestamp":1791573542062,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W007002\/1"],"award-info":[{"award-number":["MR\/W007002\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019147","name":"Universit\u00e4tsmedizin G\u00f6ttingen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019147","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp;amp; Dem Diag Ass &amp;amp; Dis Mo"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Dementia is a rising global health challenge. Advances in large\u2010scale proteomics and genetic databases have enabled high\u2010throughput screening approaches to uncover novel mechanistic pathways and therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      This study used a Mendelian randomization framework to examine genetic associations of 2172 plasma proteins (UK Biobank,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a054,219) with: (1) dementia subtypes (FinnGen,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0429,209), including Alzheimer's disease (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a012,348), vascular dementia (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a02667), and Parkinson's disease dementia (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0589); and (2) global neuroimaging markers (UK Biobank), including white matter hyperintensities (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a042,310), fractional anisotropy (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a017,663), and mean diffusivity (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a017,467).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULT<\/jats:title>\n                    <jats:p>Multiple potential causal protein\u2013outcome relationships were identified, corroborating known associations (e.g., apolipoprotein E, synaptosomal\u2010associated protein 25) and uncovering more novel proteins (e.g., butyrophilin subfamily 3 member A2, granzyme A, contactin\u20102, and trefoil factor 3) potentially involved in dementia disease processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>The identified proteins have diverse functions spanning immune regulation, cellular proliferation, neuronal stability, and neuroinflammation. The findings increase our understanding of disease processes governing cognitive health and highlight candidate proteins with potential as new disease biomarkers or therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>We used Mendelian randomization to link 2172 plasma proteins to dementia and brain imaging traits.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Apolipoprotein E, triggering receptor expressed on myeloid cells 2, and Fc receptor\u2010like 3 showed protective associations across dementia subtypes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Butyrophilin subfamily 3 member A2, granzyme A, contactin\u20102, and trefoil factor 3 were uncovered as novel dementia\u2010associated proteins.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Immune, metabolic, and vascular pathways were implicated in the etiology of dementia.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dad2.70202","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T18:21:02Z","timestamp":1761070862000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic associations of plasma proteomics with dementia subtypes and neuroimaging markers"],"prefix":"10.1002","volume":"17","author":[{"given":"Ahmed M.","family":"Salih","sequence":"first","affiliation":[{"name":"William Harvey Research Institute National Institute for Health Research Barts Biomedical Research Centre Queen Mary University of London London UK"},{"name":"Department of Population Health Sciences University of Leicester Leicester UK"},{"name":"PRIME Lab Scientific Research Centre University of Zakho  Zakho Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janek","family":"Salatzki","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute National Institute for Health Research Barts Biomedical Research Centre Queen Mary University of London London UK"},{"name":"Department of Cardiology Angiology and Pneumology Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre University of Leicester Leicester UK"},{"name":"National Institute for Health Research Leicester Biomedical Research Centre University of Leicester and University Hospitals of Leicester NHS Trust Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tesfamariam","family":"Akilu","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute National Institute for Health Research Barts Biomedical Research Centre Queen Mary University of London London UK"},{"name":"Department of Cardiology, College of Health Sciences Addis Ababa University Addis Ababa Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Maldonado","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute National Institute for Health Research Barts Biomedical Research Centre Queen Mary University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masud","family":"Husain","sequence":"additional","affiliation":[{"name":"Wellcome Centre for 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