{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T10:28:17Z","timestamp":1767004097277,"version":"3.48.0"},"posted":{"date-parts":[[2025,12,22]]},"group-title":"Genomics","reference-count":74,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01 AG067592"],"award-info":[{"award-number":["R01 AG067592"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01 AG070897"],"award-info":[{"award-number":["R01 AG070897"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["P30 AG072931"],"award-info":[{"award-number":["P30 AG072931"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"crossref","award":["P42 ES017198"],"award-info":[{"award-number":["P42 ES017198"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Dementia is a public health challenge and exposures likely contribute to risk, though many have not been evaluated. We screened chemicals for enrichment with dementia genes and related pathways.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We obtained gene lists from the Comparative Toxicogenomics Database for 1,008 chemicals and nine dementia-related pathways (e.g., Alzheimer\u2019s disease, tauopathies). We tested pairwise chemical-dementia gene enrichment using Fisher\u2019s exact tests and proportional reporting ratios (PRR), accounting for multiple comparisons with false discovery rate (FDR&lt;1\u00d710\n                    <jats:sup>-<\/jats:sup>\n                    <jats:sup>6<\/jats:sup>\n                    ).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of the chemicals tested, 742 (73.6%) were enriched for at least one dementia pathway and 15 with all nine pathways, including benzo(a)pyrene, ethanol, paraquat, and particulate matter. We observed 295 chemicals enriched for Alzheimer\u2019s disease, including sodium arsenite (PRR = 57.9) and 305 enriched for tauopathies, including bisphenol A (PRR=37.7).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>We identified chemicals enriched for dementia pathways, suggesting broad classes of chemicals contribute to dementia.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.19.695572","type":"posted-content","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T01:50:19Z","timestamp":1766454619000},"source":"Crossref","is-referenced-by-count":0,"title":["Identification of chemicals targeting dementia genes and pathways in the Comparative Toxicogenomics Database"],"prefix":"10.64898","author":[{"given":"Scarlet","family":"Cockell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean M.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel K.","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary J.","family":"Patti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin B.","family":"Ware","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9605-6337","authenticated-orcid":false,"given":"Kelly M.","family":"Bakulski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.1","DOI":"10.1016\/j.smrv.2014.03.007"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.2","DOI":"10.31887\/DCNS.2009.11.2\/cqiu"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.3","DOI":"10.37765\/ajmc.2022.89236"},{"unstructured":"Alzheimer\u2019s Association 2025 Alzheimer\u2019s Disease Facts and Figures.","key":"2025122902250901000_2025.12.19.695572v2.4"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.5","DOI":"10.1016\/j.cell.2022.12.032"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.6","DOI":"10.1093\/jnen\/nlz129"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.7","DOI":"10.1038\/s41419-022-05153-5"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.8","DOI":"10.1038\/s41588-022-01024-z"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.9","DOI":"10.1016\/S0140-6736(24)01296-0"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.10","DOI":"10.3233\/JAD-221054"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.11","DOI":"10.1006\/enrs.2001.4254"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.12","DOI":"10.1289\/EHP5550"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.13","DOI":"10.3233\/JAD-150024"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.14","DOI":"10.3233\/JAD-200282"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.15","DOI":"10.1007\/s40520-024-02718-6"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.16","DOI":"10.1126\/science.aay3164"},{"unstructured":"US EPA O. Now Available: Latest Update to the TSCA Inventory. August 14, 2025. Accessed December 23, 2025. https:\/\/www.epa.gov\/chemicals-under-tsca\/now-available-latest-update-tsca-inventory-8","key":"2025122902250901000_2025.12.19.695572v2.17"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.18","DOI":"10.1021\/acs.est.9b06379"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.19","DOI":"10.1093\/nar\/gkae883"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.20","DOI":"10.1016\/j.envint.2020.105496"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.21","DOI":"10.1016\/j.nbd.2021.105360"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.22","DOI":"10.2353\/ajpath.2007.070182"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.23","DOI":"10.1093\/brain\/awad078"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.24","DOI":"10.1038\/s41582-019-0231-z"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.25","DOI":"10.1073\/pnas.83.13.4913"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.26","DOI":"10.1186\/s13024-021-00503-x"},{"unstructured":"R: The R Project for Statistical Computing. Accessed December 23, 2025. https:\/\/www.r-project.org\/","key":"2025122902250901000_2025.12.19.695572v2.27"},{"doi-asserted-by":"crossref","unstructured":"Manning C , Raghavan P , Schuetze H . Introduction to Information Retrieval. Published online 2009.","key":"2025122902250901000_2025.12.19.695572v2.28","DOI":"10.1017\/CBO9780511809071"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.29","DOI":"10.1016\/S0166-4328(01)00297-2"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.30","DOI":"10.1038\/nrneurol.2012.263"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.31","DOI":"10.1101\/cshperspect.a024539"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.32","DOI":"10.18632\/oncotarget.16490"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.33","DOI":"10.1136\/jmg.2005.033456"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.34","DOI":"10.1038\/sj.mp.4001101"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.35","DOI":"10.1016\/j.envres.2025.121007"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.36","DOI":"10.1002\/alz.14216"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.37","DOI":"10.1001\/jamanetworkopen.2024.48286"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.38","DOI":"10.1136\/jnnp-2020-322815"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.39","DOI":"10.2174\/1567205020666230206142738"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.40","DOI":"10.18332\/tid\/157208"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.41","DOI":"10.1093\/exposome\/osaf002"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.42","DOI":"10.1093\/exposome\/osaf001"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.43","DOI":"10.3233\/JAD-170658"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.44","DOI":"10.1016\/j.wasman.2024.03.017"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.45","DOI":"10.1093\/jnci\/djac242"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.46","DOI":"10.3390\/ijerph18042190"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.47","DOI":"10.1289\/EHP12768"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.48","DOI":"10.3390\/toxics11010057"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.49","DOI":"10.1177\/14034948221110019"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.50","DOI":"10.1016\/j.envint.2020.106251"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.51","DOI":"10.1186\/s12889-025-21305-6"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.52","DOI":"10.1038\/s43587-025-00844-y"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.53","DOI":"10.1016\/j.scitotenv.2024.174202"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.54","DOI":"10.1016\/j.arr.2023.101862"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.55","DOI":"10.1016\/j.euroneuro.2013.03.007"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.56","DOI":"10.1016\/j.cotox.2018.12.007"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.57","DOI":"10.1016\/j.bbrc.2008.05.052"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.58","DOI":"10.1001\/jamaneurol.2023.0697"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.59","DOI":"10.1186\/s13024-025-00811-6"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.60","DOI":"10.1007\/s00125-014-3257-1"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.61","DOI":"10.3390\/ijms23020616"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.62","DOI":"10.1186\/s12974-020-01925-y"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.63","DOI":"10.1007\/s00213-024-06697-4"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.64","DOI":"10.3390\/toxics9080188"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.65","DOI":"10.1001\/jama.2023.23784"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.66","DOI":"10.1016\/j.jagp.2024.01.025"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.67","DOI":"10.1016\/j.ecoenv.2021.113041"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.68","DOI":"10.1523\/JNEUROSCI.4405-07.2008"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.69","DOI":"10.1016\/j.tox.2022.153376"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.70","DOI":"10.3233\/JAD-2012-111853"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.71","DOI":"10.3389\/fnagi.2022.955878"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.72","DOI":"10.1016\/j.jtemb.2025.127599"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.73","DOI":"10.1177\/1060028019900504"},{"doi-asserted-by":"publisher","key":"2025122902250901000_2025.12.19.695572v2.74","DOI":"10.1007\/s40520-024-02893-6"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2025.12.19.695572","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T10:25:20Z","timestamp":1767003920000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2025.12.19.695572"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,22]]},"references-count":74,"URL":"https:\/\/doi.org\/10.64898\/2025.12.19.695572","relation":{},"subject":[],"published":{"date-parts":[[2025,12,22]]},"subtype":"preprint"}}