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Mutations in the\n                  <jats:italic>Presenilin<\/jats:italic>\n                  genes contribute to AD\/ADRD, with Presenilin 1 acting as the catalytic subunit of the \u03b3-secretase complex responsible for cleaving Notch and amyloid precursor protein (APP). We hypothesized that PAE disrupts \u03b3-secretase activity during brain development, which persists and is associated with behavioral deficits later in life. Pregnant wild-type B6129 and 3xTg-AD mice were fed an ethanol-containing liquid diet during gestational days 13\u201315. From birth to adulthood, PAE increased APP C-terminal fragments and Notch intracellular domain (NICD) levels in cortical lysates. These changes were associated with impaired hippocampal-dependent learning and memory in wild-type mice at 3 and 6 months of age and exacerbated behavioral deficits in 4-month-old 3xTg-AD mice. Our findings provide the first mechanistic insight linking PAE to AD\/ADRD vulnerability.\n                <\/jats:p>","DOI":"10.64898\/2026.06.11.731622","type":"posted-content","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T21:25:19Z","timestamp":1781558719000},"source":"Crossref","is-referenced-by-count":0,"title":["Prenatal Alcohol Exposure Disrupts \u03b3-Secretase Activity and Impairs Learning and Memory in Wild-Type and 3xTg-AD Mice"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7521-1206","authenticated-orcid":false,"given":"Paola","family":"Montenegro","sequence":"first","affiliation":[{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikayla","family":"Zedek","sequence":"additional","affiliation":[{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Chicas","sequence":"additional","affiliation":[{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermes","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026061711351282000_2026.06.11.731622v1.1","doi-asserted-by":"publisher","DOI":"10.3390\/BRAINSCI12121667"},{"key":"2026061711351282000_2026.06.11.731622v1.2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4335-04.2005"},{"key":"2026061711351282000_2026.06.11.731622v1.3","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1063(2000)10:1<94::AID-HIPO11>3.0.CO;2-T"},{"key":"2026061711351282000_2026.06.11.731622v1.4","doi-asserted-by":"publisher","DOI":"10.1097\/01.wad.0000201854.62116.d7"},{"key":"2026061711351282000_2026.06.11.731622v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.06.038"},{"key":"2026061711351282000_2026.06.11.731622v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/J.REPROTOX.2013.04.003"},{"key":"2026061711351282000_2026.06.11.731622v1.7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2011.01465.x"},{"key":"2026061711351282000_2026.06.11.731622v1.8","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS22168785"},{"key":"2026061711351282000_2026.06.11.731622v1.9","doi-asserted-by":"publisher","DOI":"10.1111\/ACER.14325"},{"key":"2026061711351282000_2026.06.11.731622v1.10","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5110-07.2008"},{"key":"2026061711351282000_2026.06.11.731622v1.11","doi-asserted-by":"publisher","DOI":"10.1097\/GRF.0000000000000414"},{"key":"2026061711351282000_2026.06.11.731622v1.12","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhz199"},{"key":"2026061711351282000_2026.06.11.731622v1.13","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhy094"},{"key":"2026061711351282000_2026.06.11.731622v1.14","doi-asserted-by":"publisher","DOI":"10.15585\/MMWR.MM6816A1"},{"key":"2026061711351282000_2026.06.11.731622v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/BS.CTDB.2022.10.003"},{"key":"2026061711351282000_2026.06.11.731622v1.16","doi-asserted-by":"publisher","DOI":"10.5014\/AJOT.62.3.265"},{"key":"2026061711351282000_2026.06.11.731622v1.17","doi-asserted-by":"publisher","DOI":"10.1515\/NIPT-2023-0003"},{"key":"2026061711351282000_2026.06.11.731622v1.18","doi-asserted-by":"publisher","DOI":"10.3389\/FNAGI.2014.00342\/XML"},{"key":"2026061711351282000_2026.06.11.731622v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/J.FCT.2021.112105"},{"key":"2026061711351282000_2026.06.11.731622v1.20","doi-asserted-by":"publisher","DOI":"10.1080\/1029842021000010884"},{"key":"2026061711351282000_2026.06.11.731622v1.21","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-1553"},{"key":"2026061711351282000_2026.06.11.731622v1.22","doi-asserted-by":"publisher","DOI":"10.1242\/DEV.127.12.2593"},{"key":"2026061711351282000_2026.06.11.731622v1.23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.116962"},{"key":"2026061711351282000_2026.06.11.731622v1.24","unstructured":"Hill, M. 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