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Background <p>Early detection of Alzheimer's disease (AD) pathology in cognitively unimpaired individuals is critical for preclinical intervention. Plasma biomarkers, especially phosphorylated tau217 (p-tau217), are promising predictors of amyloid-β (Aβ) accumulation.</p> Methods <p>In this cohort study, we analyzed data from cognitively unimpaired older adults in the A4 and LEARN studies (<i>n</i> = 1,407), comprising 452 participants with Aβ positron emission tomography (PET)-negative status and 955 participants with Aβ PET-positive status. We evaluated the accuracy of plasma biomarkers (p-tau217, p-tau181, Aβ42/40 ratio, and others) in predicting Aβ PET positivity using receiver operating characteristic analysis, comparing covariate-adjusted individual biomarker and biomarker-ratio models with a multivariable combined model integrating plasma biomarkers and covariates. (age, sex, apolipoprotein E [APOE] ε4 genotype).</p> Results <p>Plasma p-tau217 showed the strongest individual association with Aβ PET status (area under the curve [AUC], 0.85). A combined model integrating p-tau217, p-tau181, Aβ42, age, sex, and APOE ε4 achieved the highest overall discrimination (AUC, 0.87), although the improvement over the covariate-adjusted p-tau217 model was modest.</p> Conclusions <p>Plasma p-tau217 showed the strongest individual performance for predicting Aβ PET positivity in cognitively unimpaired older adults. Adding other plasma biomarkers and clinical covariates provided a modest incremental improvement in classification performance. These findings support blood-based prescreening as a potential enrichment approach, while indicating that confirmatory amyloid assessment remains necessary when definitive Aβ status is required.</p>

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Plasma p-tau217, p-tau181, and Aβ42 predict amyloid PET positivity in cognitively unimpaired adults

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月20日

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  • Rui Bao,
  • Wanying Shi,
  • Hongbo Bao,
  • Tonghua Zhang,
  • Xueying Li,
  • Wencai Ding,
  • Sid E O’Bryant,
  • Kristine Yaffe,
  • Arthur Toga,
  • Robert Rissman,
  • Leigh Johnson,
  • Meredith Braskie,
  • Braskie King,
  • James R Hall,
  • Melissa Petersen,
  • Raymond Palmer,
  • Robert Barber,
  • Yonggang Shi,
  • Fan Zhang,
  • Rajesh Nandy,
  • Roderick McColl,
  • David Mason,
  • Christian Bradley,
  • Nicole Phillips,
  • Stephanie Large,
  • Joe Lee,
  • Badri Vardarajan,
  • Monica Rivera Mindt,
  • Amrita Cheema,
  • Lisa Barnes,
  • Mark Mapstone,
  • Annie Cohen,
  • Amy Kind,
  • Ozioma Okonkwo,
  • Raul Vintimilla,
  • Zhengyang Zhou,
  • Michael Donohue,
  • Rema Raman,
  • Matthew Borzage,
  • Michelle Mielke,
  • Beau Ances,
  • Ganesh Babulal,
  • Jorge Llibre-Guerra,
  • Carl Hill,
  • Rocky Vig

摘要

Background

Early detection of Alzheimer's disease (AD) pathology in cognitively unimpaired individuals is critical for preclinical intervention. Plasma biomarkers, especially phosphorylated tau217 (p-tau217), are promising predictors of amyloid-β (Aβ) accumulation.

Methods

In this cohort study, we analyzed data from cognitively unimpaired older adults in the A4 and LEARN studies (n = 1,407), comprising 452 participants with Aβ positron emission tomography (PET)-negative status and 955 participants with Aβ PET-positive status. We evaluated the accuracy of plasma biomarkers (p-tau217, p-tau181, Aβ42/40 ratio, and others) in predicting Aβ PET positivity using receiver operating characteristic analysis, comparing covariate-adjusted individual biomarker and biomarker-ratio models with a multivariable combined model integrating plasma biomarkers and covariates. (age, sex, apolipoprotein E [APOE] ε4 genotype).

Results

Plasma p-tau217 showed the strongest individual association with Aβ PET status (area under the curve [AUC], 0.85). A combined model integrating p-tau217, p-tau181, Aβ42, age, sex, and APOE ε4 achieved the highest overall discrimination (AUC, 0.87), although the improvement over the covariate-adjusted p-tau217 model was modest.

Conclusions

Plasma p-tau217 showed the strongest individual performance for predicting Aβ PET positivity in cognitively unimpaired older adults. Adding other plasma biomarkers and clinical covariates provided a modest incremental improvement in classification performance. These findings support blood-based prescreening as a potential enrichment approach, while indicating that confirmatory amyloid assessment remains necessary when definitive Aβ status is required.