{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:45:27Z","timestamp":1790217927386,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007625","name":"Cure Alzheimer's Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM007748"],"award-info":[{"award-number":["T32GM007748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Alzheimer's disease (AD) is the most common form of dementia in the elderly. Given that AD neuropathology begins decades before symptoms, there is a dire need for effective screening tools for early detection of AD to facilitate early intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Here, we used tree\u2010based and deep learning methods to train polyomic prediction models for AD affection status and age at onset, employing genomic, proteomic, metabolomic, and drug use data from UK Biobank. We used SHAP to determine the feature's importance.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Our best\u2010performing polyomic model achieved an area under the receiver operating characteristics curve (AUROC) of 0.87. We identified GFAP and CXCL17 proteins to be the strongest predictors of AD, besides <jats:italic>apolipoprotein E<\/jats:italic> (<jats:italic>APOE)<\/jats:italic> alleles. Increasing the number of cases by including \u201cAD\u2010by\u2010proxy\u201d cases did not improve AD prediction.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Among the four modalities, genomics, and proteomics were the most informative modality based on AUROC (area under the receiver operating characteristic curve). Our data suggest that two blood\u2010based biomarkers (glial fibrillary acidic protein [GFAP] and CXCL17) may be effective for early presymptomatic prediction of AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>We developed a polyomic model to predict AD and age\u2010at\u2010onset using omics and medication use data from EHR.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We identified GFAP and CXCL17 proteins to be the strongest predictors of AD, besides <jats:italic>APOE<\/jats:italic> alleles.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>\u201cAD\u2010by\u2010proxy\u201d cases, if used in training, do not improve AD prediction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Proteomics was the most informative modality overall for affection status and AAO prediction.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14319","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T01:25:25Z","timestamp":1731029125000},"page":"8700-8714","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Assessing polyomic risk to predict Alzheimer's disease using a machine learning model"],"prefix":"10.1002","volume":"20","author":[{"given":"Tiffany","family":"Ngai","sequence":"first","affiliation":[{"name":"Department of Neurology Genetics and Aging Research Unit and the McCance Center for Brain Health Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"},{"name":"Department of Systems Design Engineering University of Waterloo  Waterloo Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Willett","sequence":"additional","affiliation":[{"name":"Department of Neurology Genetics and Aging Research Unit and the McCance Center for Brain Health Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Waqas","sequence":"additional","affiliation":[{"name":"Department of Neurology Genetics and Aging Research Unit and the McCance Center for Brain Health Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas H.","family":"Fishbein","sequence":"additional","affiliation":[{"name":"Department of Neurology Genetics and Aging Research Unit and the McCance Center for Brain Health Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younjung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Neurology Genetics and Aging Research Unit and the McCance Center for Brain Health Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Hahn","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Mullin","sequence":"additional","affiliation":[{"name":"Department of Neurology Genetics and Aging Research Unit and the McCance Center for Brain Health Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Lange","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Biostatistics Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Hecker","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolph E.","family":"Tanzi","sequence":"additional","affiliation":[{"name":"Department of Neurology Genetics and Aging Research Unit and the McCance Center for Brain Health Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1844-5652","authenticated-orcid":false,"given":"Dmitry","family":"Prokopenko","sequence":"additional","affiliation":[{"name":"Department of Neurology Genetics and Aging Research Unit and the McCance Center for Brain Health Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12694"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(21)00249-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201911170"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2021.23"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S394821"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001991"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010024\u201002869\u2010z"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2021.107739"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.aivir.2017.02.001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3314"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389202922666210705124359"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad373"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74399-w"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eswa.2019.112873"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/ETLS20210249"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/2023.06.09.23291213"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-27551-1"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002258"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-220174"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010024\u201000655\u20107"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.08.051"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00814-7"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2024.108588"},{"key":"e_1_2_9_25_1","doi-asserted-by":"crossref","first-page":"567","DOI":"10.14283\/jpad.2024.34","article-title":"Multiomics blood\u2010based biomarkers predict Alzheimer's predementia with high specificity in a multicentric cohort study","volume":"11","author":"Souchet B","year":"2024","journal-title":"J Prev Alzheimers Dis"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbinf.2024.1390607"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.22581"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbae267"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0579-z"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03205-y"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-022-02354-9"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63033"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06563-x"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06592-6"},{"key":"e_1_2_9_36_1","doi-asserted-by":"crossref","DOI":"10.3310\/hta23590","volume-title":"In: An Intervention to Improve Outcomes of Falls In Dementia: The DIFRID Mixed\u2010Methods Feasibility Study","author":"Allan LM","year":"2019"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0311-9"},{"key":"e_1_2_9_38_1","article-title":"Genetic and regulatory architecture of Alzheimer's disease in the APOE region","volume":"12","author":"Kulminski AM","year":"2020","journal-title":"Alzheimers Dement"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0495-7"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.psych.58.110405.085530"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-017-0442-1"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1013203451"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1609\/aaai.v35i8.16826"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1109\/TNNLS.2022.3229161"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00657-5"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diii.2020.05.009"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13321-023-00743-7"},{"key":"e_1_2_9_48_1","doi-asserted-by":"crossref","unstructured":"HerwantoHW HandayaniAN WibawaAP ChandrikaKL AraiK.Comparison of min\u2010max Z\u2010score and decimal scaling normalization for zoning feature extraction on Javanese character recognition. In:2021 7th International Conference on Electrical Electronics and Information Engineering (ICEEIE).IEEE;2021. doi:10.1109\/iceeie52663.2021.9616665","DOI":"10.1109\/ICEEIE52663.2021.9616665"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/87.4.954"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2202113119"},{"key":"e_1_2_9_51_1","unstructured":"LundbergS LeeS\u2010I.A unified approach to interpreting model predictions. In:NIPS'17: Proceedings of the 31st International Conference on Neural Information Processing SystemsCurran Associates Inc.;2017:4768\u20104777. doi:10.48550\/ARXIV.1705.07874"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42256-019-0138-9"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-022-00277-x"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nrl.2016.02.016"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.disamonth.2010.06.001"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25158485"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ssmph.2020.100577"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12091309"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.633297"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43575-7"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-021-00968-0"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.01.016"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.14319","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T11:28:41Z","timestamp":1759922921000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.14319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,7]]},"references-count":61,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/alz.14319"],"URL":"https:\/\/doi.org\/10.1002\/alz.14319","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,7]]},"assertion":[{"value":"2024-04-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}