{
  "abstract": "Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) frequently co-occurs with Alzheimers disease (AD) pathology and has been studied mainly in older populations. We examined its frequency and expression in 196 individuals with autopsy-confirmed intermediate-to-high AD neuropathologic change, enriched for younger-onset cases, integrating neuropathology with antemortem clinical, cognitive and neuroimaging data. LATE-NC occurred in 31% overall and 19% of individuals with symptom onset [≤]65 years. Its frequency increased with older age at symptom onset, and its presence was associated with greater episodic memory impairment and smaller amygdala and hippocampal volumes. Among individuals with LATE-NC, older age at symptom onset was associated with memory-first presentation and greater medial temporal involvement, including higher inferior-to-medial temporal metabolism ratios on FDG PET. Despite its lower frequency, LATE-NC co-pathology should still be considered in early-onset AD, where selected clinical features and neuroimaging markers described in older populations may be less applicable.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "name": "Nuole Zhu",
      "orcid": "0000-0002-0015-9455"
    },
    {
      "name": "Renaud La Joie",
      "orcid": "0000-0003-2581-8100"
    },
    {
      "name": "Isabel Elaine Allen"
    },
    {
      "name": "Marlene Lin"
    },
    {
      "name": "D. Luke Fischer",
      "orcid": "0000-0002-5245-3832"
    },
    {
      "name": "David N. Soleimani-Meigooni"
    },
    {
      "name": "Howard J. Rosen",
      "orcid": "0000-0001-9281-7402"
    },
    {
      "name": "Maria Luisa Gorno-Tempini"
    },
    {
      "name": "Zachary Miller"
    },
    {
      "name": "David C. Perry"
    },
    {
      "name": "Joel Kramer"
    },
    {
      "name": "Katherine L. Possin"
    },
    {
      "name": "Yann Cobigo"
    },
    {
      "name": "Lyzzette Melgoza"
    },
    {
      "name": "Argentina Lario Lago"
    },
    {
      "name": "Jennifer Yokoyama"
    },
    {
      "name": "Claire Yballa"
    },
    {
      "name": "Ganna Blazhenets"
    },
    {
      "name": "Bruce L. Miller"
    },
    {
      "name": "Lea T. Grinberg"
    },
    {
      "name": "William W. Seeley"
    },
    {
      "name": "Salvatore Spina"
    },
    {
      "name": "Gil D. Rabinovici"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9hmmwmc2rqs4m.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.15.26365384",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.15.26365384v1.full",
  "id": "9hmmwmc2rqs4m",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.15.26365384v1",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "medrxiv",
      "neurology"
    ],
    [
      "openalex",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7223031913",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.15.26365384v1.full.pdf",
  "pmcid": "PMC13738863",
  "pmid": "42996207",
  "published": "2026-10-15",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/9hmmwmc2rqs4m.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:20Z",
      "native_id": "10.64898/2026.10.15.26365384",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.15.26365384v1"
    },
    {
      "first_seen": "2026-11-09T12:23:46Z",
      "native_id": "PMC13738863",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.15.26365384"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:neurology",
      "subfield": "neurology"
    }
  ],
  "title": "Too early for LATE? Age at onset is associated with the clinical and neuroimaging expression of limbic-predominant age-related TDP-43 pathology in Alzheimer's disease",
  "title_text": "Too early for LATE? Age at onset is associated with the clinical and neuroimaging expression of limbic-predominant age-related TDP-43 pathology in Alzheimer's disease",
  "type": "preprint",
  "updated_at": "2026-11-09T12:23:46Z",
  "url": "https://research.draconitic.com/paper/9hmmwmc2rqs4m",
  "venue": "medRxiv",
  "versions": []
}