{"doi":"10.1002/alz.70916","title":"Cross‐cohort validation and cutpoint estimation of the Janssen plasma p‐tau217+ assay in predominantly cognitively normal community studies","abstract":"INTRODUCTION: Cross-cohort validation studies for plasma phosphorylated tau (p-tau) 217 are limited. We evaluated the Janssen plasma p-tau217+ assay and proposed a cutpoint value in three independent community-based cohorts. METHODS: We included n = 441 participants (age = 70.3 ± 7.3) from three independent community-based cohorts with amyloid-beta-positron emission tomography (Aβ-PET), tau-PET, clinical, and cognitive information. RESULTS: The cohorts had low pre-test probability (%Aβ positivity = 14.9-24.7) and were predominantly cognitively normal (> 73%). Plasma p-tau217+ had high accuracy for abnormal Aβ PET (areas under the curve [AUCs] = 81-86%), good correlation with Aβ-PET burden (0.336-0.397) that was highest in the cohort with the most Aβ-PET-positive participants, and the biomarker concentrations were highest in the joint Aβ-PET and tau-PET positive group. Negative predictive value (NPV) was high across cohorts (≤93%) but positive predictive value (PPV) was consistently poor (< 57%). Sensitivity and specificity averaged 75% and 84%, respectively. A combined cohort cutpoint of 0.05pg/ml gave AUC = 84.5%, NPV = 94%, PPV = 50%, sensitivity = 75%, and specificity = 84%. DISCUSSION: Plasma p-tau217+ can rule out Aβ pathophysiology due to Alzheimer's disease at the population level. Cohort-level %Aβ-PET positivity influences accuracies. HIGHLIGHTS: Plasma phosphorylated tau (p-tau) 217 assays have demonstrated potential to identify older adults with brain amyloid pathology due to Alzheimer's disease. Community-based studies are crucial for accessing the clinical validity of fluid biomarkers and their real-world applicability. We evaluated the Janssen plasma p-tau217+ assay in three community-based cohorts. Janssen plasma p-tau217+ identified amyloid-beta abnormalities across three diverse cohorts of community-dwelling older adults. High NPV indicates p-tau217+ as a good tool for initial screening to enrich for high-risk individuals particularly for cohort studies and clinical trial participation.","journal":"Alzheimer s & Dementia","year":2025,"id":548816,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6273,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":518875,"name":"Xuemei Zeng","orcid":"0000-0003-4885-4788","position":1,"is_corresponding":false},{"id":353468,"name":"Gallen Triana‐Baltzer","orcid":"0000-0003-0612-1236","position":2,"is_corresponding":false},{"id":486701,"name":"Anum Saeed","orcid":"0000-0003-1783-678X","position":3,"is_corresponding":false},{"id":1442984,"name":"Happiness E. Aigbogun","orcid":null,"position":4,"is_corresponding":false},{"id":813235,"name":"Alexandra Gogola","orcid":"0000-0002-8798-1715","position":5,"is_corresponding":false},{"id":422874,"name":"Brian J. Lopresti","orcid":"0000-0002-0595-0203","position":6,"is_corresponding":false},{"id":236168,"name":"Victor L. Villemagne","orcid":"0000-0002-5832-9875","position":7,"is_corresponding":false},{"id":251490,"name":"Mary Ganguli","orcid":"0000-0003-2762-7105","position":8,"is_corresponding":false},{"id":74385,"name":"Hartmuth C. Kolb","orcid":"0000-0003-2414-5792","position":9,"is_corresponding":false},{"id":251492,"name":"Beth E. Snitz","orcid":"0000-0002-9978-1374","position":10,"is_corresponding":false},{"id":279707,"name":"Oscar L. Lopez","orcid":null,"position":11,"is_corresponding":false},{"id":329924,"name":"Ann D. Cohen","orcid":"0000-0001-7395-9624","position":12,"is_corresponding":false},{"id":413400,"name":"Steven E. 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