{
  "abstract": "Although prenatal alcohol exposure (PAE) has been proposed as an early- life risk factor for Alzheimer's disease and related dementias (AD/ADRD), the mechanistic underpinnings are underexplored. Mutations in the Presenilin genes contribute to AD/ADRD, with Presenilin 1 acting as the catalytic subunit of the gamma-secretase complex responsible for cleaving Notch and amyloid precursor protein (APP). We hypothesized that PAE disrupts gamma-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 13-15. From birth to adulthood, PAE increased APP C-terminal fragments and Notch intracellular domain (NICD) levels in cortical lysates. These changes were accompanied by 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.",
  "abstract_shown": true,
  "affiliations": [
    "Dartmouth College"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "P. C. Montenegro"
    },
    {
      "name": "R. Kim"
    },
    {
      "name": "M. Zedek"
    },
    {
      "name": "M. Chicas"
    },
    {
      "name": "P. W. L. Yeh"
    },
    {
      "name": "H. H. Yeh"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2jktk14qmaabj.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.06.11.731622",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.06.11.731622v2.full",
  "id": "2jktk14qmaabj",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.06.11.731622v2",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.06.11.731622v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2jktk14qmaabj.ris",
  "sources": [
    {
      "first_seen": "2026-11-12T00:23:38Z",
      "native_id": "10.64898/2026.06.11.731622",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.06.11.731622v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Prenatal Alcohol Exposure Disrupts γ-Secretase Activity and Impairs Learning and Memory in Wild-Type and 3xTg-AD Mice",
  "title_text": "Prenatal Alcohol Exposure Disrupts γ-Secretase Activity and Impairs Learning and Memory in Wild-Type and 3xTg-AD Mice",
  "type": "preprint",
  "updated_at": "2026-11-13T00:23:20Z",
  "url": "https://research.draconitic.com/paper/2jktk14qmaabj",
  "venue": "bioRxiv",
  "versions": []
}