{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:00:04Z","timestamp":1760058004401,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R21AG046701","R01AG077395","1R35GM138212"],"award-info":[{"award-number":["R21AG046701","R01AG077395","1R35GM138212"]}]},{"name":"National Institute of Aging","award":["R21AG046701","R01AG077395","1R35GM138212"],"award-info":[{"award-number":["R21AG046701","R01AG077395","1R35GM138212"]}]},{"name":"National Institute of General Medical Sciences","award":["R21AG046701","R01AG077395","1R35GM138212"],"award-info":[{"award-number":["R21AG046701","R01AG077395","1R35GM138212"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a leading cause of dementia in the elderly, with late-onset AD (LOAD) accounting for 95% of the cases. The etiology underlying LOAD, however, remains unclear. Using a humanized mouse model, we showed previously that exposure to ozone (O3), a potential environment risk factor, in a cyclic exposure protocol that mimics a human exposure scenario, accelerated AD-like neuropathophysiology in old humanized male ApoE3 (E3) but not ApoE4 (E4) mice. Using RNA sequencing (RNA-seq) techniques, we further demonstrate here that the ApoE genotype has the greatest influence on transcriptional changes, followed by age and O3 exposure. Notably, AD-related genes were expressed even at baseline and in young mice, but the differences in the expression levels are obvious in old age. Importantly, although both E3 and E4 mice exhibited some AD-related transcriptomic alterations, old E3 mice exposed to O3, which showed memory impairment, experienced more pronounced disruptions in the expression of genes related to redox balance, neurogenesis, neuroinflammation, and cellular senescence in the hippocampus, compared with O3-exposed old E4 mice. These results provide new insights into the molecular mechanisms underlying memory loss in O3-exposed old E3 male mice and emphasize the complexity of interactions between gene, environment, and aging in AD pathophysiology.<\/jats:p>","DOI":"10.3390\/ijms26062407","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T09:38:46Z","timestamp":1741340326000},"page":"2407","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age- and ApoE Genotype-Dependent Transcriptomic Responses to O3 in the Hippocampus of Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Mary F.","family":"Nakamya","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9461-1328","authenticated-orcid":false,"given":"Kaili","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics and Data Science, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunsun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zechen","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics and Data Science, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0751-5579","authenticated-orcid":false,"given":"Rui-Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2023). 2023 Alzheimer\u2019s disease facts and figures. 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