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Residential zip code and 2009\u20132021 EPA-based annual AP reports were used to estimate individual exposure. Cox proportional hazards models assessed MCI\/AD risk. Linear regressions examined the relationships between AP exposure and biomarkers of core and AD-relevant pathology, with and without APOE4\u2009+\u2009stratification. Causal mediation analysis examined whether markers of inflammation mediated the AP-AD pathology relationships.\u00a0Neither O\u2083 nor PM\u2082.\u2085 exposure predicted MCI\/AD incidence nor core AD pathology (Ps\u2009&gt;\u20090.05). Higher PM\u2082.\u2085 was associated with higher CSF GFAP levels (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.003). APOE4\u2009+\u2009with higher levels of PM\u2082.\u2085 exposure had higher CSF levels of tTau (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.01), pTau\u2081\u2088\u2081 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.01) and neurogranin (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.02). These relationships were not mediated by neuroinflammation (Ps\u2009&gt;\u20090.05).\u00a0In this AD-risk enriched cohort, AP was not associated with MCI\/AD incidence. However, higher PM\u2082.\u2085 exposure was associated with astrocytic activation, and in APOE4+, AD pathology, neurodegeneration, and synaptic dysfunction. Our findings suggest AP as an environmental risk factor contributing to AD-relevant pathology, particularly among genetically at-risk individuals.\n                  <\/jats:p>","DOI":"10.1007\/s12640-026-00786-2","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T10:34:05Z","timestamp":1775558045000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations between air pollution and markers of neuroinflammation, synaptic dysfunction and core Alzheimer\u2019s disease pathology vary by APOE genotype"],"prefix":"10.1007","volume":"44","author":[{"given":"Kana","family":"Kimura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Driscoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Shahzad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobey J.","family":"Betthauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sterling C.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Asthana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine L.","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce P.","family":"Hermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Sager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia M.","family":"Carlsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendlyn","family":"Kollmorgen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozioma C.","family":"Okonkwo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"786_CR1","doi-asserted-by":"publisher","unstructured":"Alzheimer\u2019s disease facts and figures (2024) Alzheimer\u2019s & dementia: the journal of the Alzheimer\u2019s Association, 20(5), 3708\u20133821. https:\/\/doi.org\/10.1002\/alz.13809","DOI":"10.1002\/alz.13809"},{"key":"786_CR2","doi-asserted-by":"publisher","first-page":"106864","DOI":"10.1016\/j.envint.2021.106864","volume":"157","author":"S Alemany","year":"2021","unstructured":"Alemany S, Crous-Bou M, Vilor-Tejedor N, Mil\u00e0-Alom\u00e0 M, Su\u00e1rez-Calvet M, Salvad\u00f3 G, Cirach M, Arenaza-Urquijo EM, Sanchez-Benavides G, Grau-Rivera O, Minguillon C, Fauria K, Kollmorgen G, Domingo Gispert J, Gasc\u00f3n M, Nieuwenhuijsen M, Zetterberg H, Blennow K, Sunyer J, Molinuevo L, J (2021) Associations between air pollution and biomarkers of Alzheimer\u2019s disease in cognitively unimpaired individuals. 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