{
  "abstract": "Introduction\n\nPlasma phosphorylated tau (p-tau)217 is increasingly used to triage amyloid testing, but the biological and clinical meaning of discordant plasma p-tau217 and amyloid positron emission tomography (PET) results in cognitively normal adults remains uncertain.Methods\n\nWe analyzed cognitively normal participants from the Chinese Preclinical Alzheimer's Disease Study (CPAS; n = 594) and the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 475). Amyloid PET positivity was defined as Centiloid ≥ 20. Cohort-specific p-tau217 positivity was defined using PET-anchored cutoffs with ≥ 0.90 specificity, yielding four p-tau/PET groups. Linear models assessed cross-sectional biomarker and cognitive differences; mixed-effects and Cox models assessed ADNI longitudinal Centiloid accumulation, cognitive trajectories, and clinical progression.Results\n\nIn cross-sectional analyses, compared to p-tau-/PET-, p-tau+/PET- had higher glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) levels across cohorts; p-tau-/PET+ showed a lower plasma amyloid beta 42/40 ratio in ADNI; and p-tau+/PET+ showed the broadest multimodal abnormalities. In ADNI, both p-tau+ groups had higher clinical progression risk and faster decline in selected cognitive domains; both PET+ groups showed faster Centiloid accumulation. Faster Centiloid accumulation in p-tau+/PET- was observed only at lower specificity thresholds.Discussion\n\nDiscordant plasma p-tau217 and amyloid PET results should be interpreted according to both the positivity pattern and the p-tau217 cutoff applied. Distinguishing these patterns may aid risk stratification and longitudinal monitoring. Different p-tau217 operating points may support risk enrichment and prioritization for confirmatory amyloid testing, but require validation before clinical use.",
  "abstract_shown": true,
  "affiliations": [
    "Health Management Center, Shenzhen Qianhai Taikang Hospital, Shenzhen, China.",
    "Department of Gerontology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
    "Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yanlu Huang"
    },
    {
      "affs": [
        1
      ],
      "name": "Lin Huang"
    },
    {
      "affs": [
        1
      ],
      "name": "Liang Cui"
    },
    {
      "affs": [
        1
      ],
      "name": "Fengfeng Pan"
    },
    {
      "affs": [
        2
      ],
      "name": "Fang Xie",
      "orcid": "0000-0003-2667-281X"
    },
    {
      "name": "Hongbo Guo"
    },
    {
      "affs": [
        1
      ],
      "name": "Qihao Guo"
    },
    {
      "name": "Alzheimer's Disease Neuroimaging Initiative"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fg4rcr8amctze.bib",
  "cited_by": 0,
  "doi": "10.1002/alz.71922",
  "fulltext_url": "https://europepmc.org/articles/PMC13683553",
  "id": "fg4rcr8amctze",
  "issns": [
    "1552-5260",
    "1552-5279"
  ],
  "landing_url": "https://europepmc.org/article/MED/42902436",
  "language": "eng",
  "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": [
    [
      "openalex",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7223003962",
  "pdf_url": "https://europepmc.org/articles/PMC13683553?pdf=render",
  "pmcid": "PMC13683553",
  "pmid": "42902436",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fg4rcr8amctze.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42902436",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42902436"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Dementia and Cognitive Impairment Research",
      "subfield": "psychiatry"
    }
  ],
  "title": "Direction-specific biomarker profiles and clinical significance of plasma p-tau217/amyloid PET discordance in cognitively normal adults.",
  "title_text": "Direction-specific biomarker profiles and clinical significance of plasma p-tau217/amyloid PET discordance in cognitively normal adults.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/fg4rcr8amctze",
  "venue": "Alzheimer's & dementia : the journal of the Alzheimer's Association",
  "versions": []
}