{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:17:29Z","timestamp":1786976249803,"version":"build-2736575974"},"reference-count":73,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["T32MH087004"],"award-info":[{"award-number":["T32MH087004"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG061382"],"award-info":[{"award-number":["AG061382"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG061382\u201002S1"],"award-info":[{"award-number":["AG061382\u201002S1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["A2018213S"],"award-info":[{"award-number":["A2018213S"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020437","name":"Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. Louis","doi-asserted-by":"publisher","award":["P01AG003991"],"award-info":[{"award-number":["P01AG003991"]}],"id":[{"id":"10.13039\/100020437","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020437","name":"Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. Louis","doi-asserted-by":"publisher","award":["P30AG066444"],"award-info":[{"award-number":["P30AG066444"]}],"id":[{"id":"10.13039\/100020437","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Recent work has bolstered the possibility that peripheral changes may be relevant to Alzheimer's disease pathogenesis in the brain. While age\u2010associated blood\u2010borne proteins have been targeted to restore function to the aged brain, it remains unclear whether other dysfunctional systemic states can be exploited for similar benefits. Here, we investigate whether\n                      <jats:italic>APOE<\/jats:italic>\n                      allelic variation or presence of brain amyloid are associated with plasma proteomic changes and the molecular processes associated with these changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using the SOMAscan assay, we measured 1305 plasma proteins from 53 homozygous,\n                      <jats:italic>APOE3<\/jats:italic>\n                      and\n                      <jats:italic>APOE4<\/jats:italic>\n                      subjects without dementia. We investigated the relationship of either the\n                      <jats:italic>APOE\u2010\u03b54<\/jats:italic>\n                      allele or amyloid positivity with plasma proteome changes by linear mixed effects modeling and ontology\u2010based pathway and module\u2013trait correlation analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>APOE4<\/jats:italic>\n                      is associated with plasma protein differences linked to atherosclerosis, tyrosine kinase activity, cholesterol transport, extracellular matrix, and synaptogenesis pathways. Independent of\n                      <jats:italic>APOE4<\/jats:italic>\n                      , we found that subjects likely harboring brain amyloid exhibit plasma proteome signatures associated with AD\u2010linked pathways, including neurovascular dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Our results indicate that\n                      <jats:italic>APOE4<\/jats:italic>\n                      status or presence of brain amyloid are associated with plasma proteomic shifts prior to the onset of symptoms, suggesting that systemic pathways in certain risk contexts may be plausible targets for disease modification.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.52250","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T13:19:29Z","timestamp":1734441569000},"page":"366-382","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<i>APOE<\/i>\n                    genotype and brain amyloid are associated with changes in the plasma proteome in elderly subjects without dementia"],"prefix":"10.1002","volume":"12","author":[{"given":"Sarah M.","family":"Philippi","sequence":"first","affiliation":[{"name":"Nash Family Department of Neuroscience, Department of Neurology, Friedman Brain Institute Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Ronald M. Loeb Center for Alzheimer's Disease Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Graduate School of Biomedical Sciences Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Black Family Stem Cell Institute Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailash","family":"BP","sequence":"additional","affiliation":[{"name":"Nash Family Department of Neuroscience, Department of Neurology, Friedman Brain Institute Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Ronald M. Loeb Center for Alzheimer's Disease Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Graduate School of Biomedical Sciences Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Towfique","family":"Raj","sequence":"additional","affiliation":[{"name":"Nash Family Department of Neuroscience, Department of Neurology, Friedman Brain Institute Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Ronald M. Loeb Center for Alzheimer's Disease Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8026-6292","authenticated-orcid":false,"given":"Joseph M.","family":"Castellano","sequence":"additional","affiliation":[{"name":"Nash Family Department of Neuroscience, Department of Neurology, Friedman Brain Institute Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Ronald M. Loeb Center for Alzheimer's Disease Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Black Family Stem Cell Institute Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.12.003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000492573"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22067"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0673-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10357"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3569"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2499-y"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00373-6"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70325-2"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002156"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0228-7"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01548-0"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01127-0"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0337-1"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0815-6"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12286"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abq5923"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13023"},{"key":"e_1_2_9_21_1","doi-asserted-by":"crossref","unstructured":"KaurG 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