{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T07:46:41Z","timestamp":1776930401487,"version":"3.51.2"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Dement."],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex neurodegenerative disorder influenced by various factors, including genetic and exposure-related. Certain combinations of these factors may promote AD more substantially than others. APOE4 is the strongest genetic risk factor for AD. Traffic-related air pollution (TRAP) and infections are important exposure-related AD risk factors. Here we investigated how the interplay between a history of infections and chronically high exposure to TRAP (highTRAP) impacts the subsequent risk of AD and other dementias (AD+) in carriers and non-carriers of APOE4 in UK Biobank (UKB) participants aged 60\u201375\u202fyears. HighTRAP was approximated by the proximity (50 meters or less) of a participant\u2019s primary residence to a major road. Chi-square, Wilson score interval, Wald interval, Wald risk ratio, Welch tests, and regression were used to examine statistical significance. We found that UKB participants with a history of various infections (by ICD-10 codes), but without highTRAP, had a 54% increase in AD+ risk. HighTRAP alone did not significantly influence AD+ risk. Individuals with both a history of infections and highTRAP had a 164% higher risk of AD+ compared to those without either factor. That risk was much higher (349%) in non-carriers of APOE4 but became non-significant in APOE4 carriers. We conclude that avoiding high exposure to TRAP may significantly reduce the risk of AD in non-carriers of APOE4 with a history of infections but not in carriers. One potential explanation could be that APOE4 is a stronger AD risk factor, whose AD-promoting effects may outweigh those of other risk factors.<\/jats:p>","DOI":"10.3389\/frdem.2025.1668381","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T14:31:14Z","timestamp":1768228274000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Traffic-related air pollution significantly aggravates the detrimental effect of infections on the risk of Alzheimer\u2019s disease and other dementias, especially in non-carriers of APOE4"],"prefix":"10.3389","volume":"4","author":[{"given":"Vladimir A.","family":"Popov","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Ukraintseva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongzhe","family":"Duan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arseniy","family":"Yashkin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Kravchenko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Akushevich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Whitson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantin G.","family":"Arbeev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anatoliy I.","family":"Yashin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref2","doi-asserted-by":"publisher","first-page":"1347987","DOI":"10.3389\/fnagi.2024.1347987","article-title":"The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets","volume":"16","author":"Adamu","year":"2024","journal-title":"Front. 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