{
  "abstract": "INTRODUCTIONPlasma p-tau217 is associated with Alzheimers disease pathology and memory performance, but its implications for memory may depend on fibrillar tau topography. We examined whether tau-PET subtype modified the association between plasma p-tau217 and memory.\n\nMETHODSWe analyzed 396 amyloid-positive, tau-positive participants spanning cognitively unimpaired, mild cognitive impairment, and dementia stages from six cohorts with tau-PET and plasma p-tau217; 301 had harmonized memory data. Tau-PET subtypes were derived using data-driven disease progression modelling. Primary cross-sectional models tested subtypexp-tau217 interactions for memory, adjusting for age, sex, education, APOE {varepsilon}4 status, and cohort. Secondary and exploratory analyses examined latent global cognition, non-memory measures, and longitudinal cognitive change.\n\nRESULTSThree tau-PET subtypes were retained: limbic-predominant, medial temporal lobe (MTL)-sparing, and posterior-predominant. Cross-sectionally, MTL-sparing participants had lower plasma p-tau217 than the other subtypes. The association between higher plasma p-tau217 and worse memory differed by subtype (interaction p=0.002) and was stronger in MTL-sparing (B=-0.191, p<0.001) than in limbic-predominant (B=-0.07, p=0.002) and posterior-predominant participants (B=-0.07, p<0.001). The interaction remained significant after additional adjustment for diagnostic group (p=0.015). This pattern also persisted after additional adjustment for PET tau burden, amyloid Centiloids, or plasma A{beta}42/40; none of these biomarkers showed comparable subtype modification. Subtype modification was also observed for a global cognitive composite (interaction p=0.004) and subsequent memory decline in an exploratory analysis conditioned on baseline memory (interaction p=0.016).\n\nDISCUSSIONTau-PET subtype modified the p-tau217-memory association, suggesting that the cognitive implications of plasma p-tau217 may vary with tau topography.",
  "abstract_shown": true,
  "affiliations": [
    "University of California, Irvine"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "L. Zheng"
    },
    {
      "name": "E. Ghanbarian"
    },
    {
      "name": "C. Albarran Morillo"
    },
    {
      "name": "K. Younes"
    },
    {
      "name": "C. M. Glover"
    },
    {
      "name": "L. A. Rabin"
    },
    {
      "name": "J. D. Grill"
    },
    {
      "name": "M. Ewers"
    },
    {
      "name": "S. A. Sajjadi"
    },
    {
      "name": "A. Ezzati"
    },
    {
      "name": "the Alzheimer's Disease Neuroimaging Initiative (ADNI)"
    },
    {
      "name": "the Health and Aging Brain (HABS-HD) Study Team"
    },
    {
      "name": "the PREVENT-AD Research Group"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/98hpwkv1qmyzn.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.25.26363629",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.25.26363629v1.full",
  "id": "98hpwkv1qmyzn",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.25.26363629v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "neurology"
    ],
    [
      "openalex",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7214572622",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.25.26363629v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/98hpwkv1qmyzn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:35Z",
      "native_id": "10.64898/2026.09.25.26363629",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.25.26363629v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:neurology",
      "subfield": "neurology"
    }
  ],
  "title": "Tau-PET subtype modifies the association between plasma p-tau217 and memory in Alzheimer's disease",
  "title_text": "Tau-PET subtype modifies the association between plasma p-tau217 and memory in Alzheimer's disease",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:35Z",
  "url": "https://research.draconitic.com/paper/98hpwkv1qmyzn",
  "venue": "medRxiv",
  "versions": []
}