Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Cross-cohort validation and cutpoint estimation of the Janssen plasma p-tau217+ assay in predominantly cognitively normal community studies.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Balogun Wasiu G, Zeng Xuemei, Triana-Baltzer Gallen, Saeed Anum, Aigbogun Happiness E, Gogola Alexandra, Lopresti Brian J, Villemagne Victor L, Ganguli Mary, Kolb Hartmuth, Snitz Beth E, Lopez Oscar L, Cohen Ann D, Reis Steven E, Karikari Thomas K
Аннотация
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.
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.