{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:15:32Z","timestamp":1785420932329,"version":"3.56.0"},"posted":{"date-parts":[[2025,10,21]]},"group-title":"Neuroscience","reference-count":60,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"award":["U01AA028710-04S1"],"award-info":[{"award-number":["U01AA028710-04S1"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P50AA017823"],"award-info":[{"award-number":["P50AA017823"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U01AA028710"],"award-info":[{"award-number":["U01AA028710"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Alcohol misuse increases Alzheimer\u2019s disease (\u0391D) risk, however the mechanisms linking these conditions are unknown. In rodents, chronic and acute ethanol increases amyloid-\u03b2 (A\u03b2), however those studies have been limited to a single sex or brain region.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This study explored how adolescent intermittent ethanol (AIE), alters A\u03b2 in multiple regions of the brain in female and male TgF344-AD rats as they age.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>From P28-P58, female and male TgF344-AD rats were administered either water (CON) or 5.0 g\/kg ethanol (AIE; 20% ethanol w\/v) via intragastric gavage on a 2-day on\/off cycle. In Experiment 1, A\u03b2 was measured in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), piriform cortex (PC), entorhinal cortex (EC), ventral hippocampus (vHPC), and dorsal hippocampus (dHPC) in 6- and 10-month-old rats. In Experiment 2, in vivo microdialysis was used in 3-month-old female rats to measure how ethanol directly modulates A\u03b2 levels in the dHPC.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In the OFC, PC, EC, vHPC, and dHPC, A\u03b240 and A\u03b242 was higher in 6-month-old female TgF344-AD rats compared to males. However, at 10 months A\u03b240 and A\u03b242 levels were only elevated in the dHPC of AIE-treated females, compared to all other groups. An acute ethanol challenge at 3 months selectively evoked a sustained increase in ISF A\u03b240 levels in AIE-treated females.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In aged females, the dHPC is a region sensitive to ethanol-associated A\u03b2 pathology. This may be due to disruptions in A\u03b2 clearance in early life, which may have an additive effect on A\u03b2 aggregation over the lifespan.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.10.20.683498","type":"posted-content","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T19:55:15Z","timestamp":1761076515000},"source":"Crossref","is-referenced-by-count":0,"title":["Adolescent intermittent ethanol exacerbates A\u03b2 with age in the dorsal hippocampus of female TgF344-AD rats"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0533-0597","authenticated-orcid":false,"given":"Stephen M.","family":"Day","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole L.","family":"Reitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5711-3709","authenticated-orcid":false,"given":"Lisa M.","family":"Savage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025102401550645000_2025.10.20.683498v1.1","doi-asserted-by":"crossref","first-page":"e70235","DOI":"10.1002\/alz.70235","article-title":"2025 Alzheimer\u2019s disease facts and figures","volume":"21","author":"[1]","year":"2025","journal-title":"Alzheimers Dement"},{"key":"2025102401550645000_2025.10.20.683498v1.2","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","year":"2018","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2025102401550645000_2025.10.20.683498v1.3","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002923"},{"key":"2025102401550645000_2025.10.20.683498v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70299-6"},{"key":"2025102401550645000_2025.10.20.683498v1.5","doi-asserted-by":"crossref","first-page":"e124","DOI":"10.1016\/S2468-2667(18)30022-7","article-title":"Contribution of alcohol use disorders to the burden of dementia in France 2008\u201313: a nationwide retrospective cohort study","volume":"3","year":"2018","journal-title":"The Lancet Public Health"},{"key":"2025102401550645000_2025.10.20.683498v1.6","doi-asserted-by":"crossref","first-page":"111380","DOI":"10.1016\/j.pscychresns.2021.111380","article-title":"Cognitive dysfunction and cerebral volumetric deficits in individuals with Alzheimer\u2019s disease, alcohol use disorder, and dual diagnosis","volume":"317","year":"2021","journal-title":"Psychiatry Res Neuroimaging"},{"key":"2025102401550645000_2025.10.20.683498v1.7","doi-asserted-by":"crossref","unstructured":"Kauko A , Engler D , Niiranen T , Ortega-Alonso A , Schnabel RB (2023) Increased risk of dementia differs across cardiovascular diseases and types of dementia \u2013 Data from a nationwide study. 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