Plasma Phosphorylated Tau 217 to Identify Preclinical Alzheimer Disease.
Обработка статьи · этапы, ошибки и управление
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.
Salvadó Gemma, Janelidze Shorena, Bali Divya, Dolado Anna Orduña, Therriault Joseph, Brum Wagner S, Pichet Binette Alexa, Stomrud Erik, Mattsson-Carlgren Niklas, Palmqvist Sebastian, Coomans Emma M, Teunissen Charlotte E, van der Flier Wiesje M, Rahmouni Nesrine, Benzinger Tammie L S, Gispert Juan Domingo, Blennow Kaj, Doré Vincent, Feizpour Azadeh, Rowe Christopher C, Alcolea Daniel, Fortea Juan, Villeneuve Sylvia, Johnson Sterling C, Rosa-Neto Pedro, Petersen Ronald C, Jack Clifford R, Schindler Suzanne E, Suárez-Calvet Marc, Ossenkoppele Rik, Hansson Oskar, ADNI, ALFA, and PREVENT-AD Study Groups
Аннотация
OBJECTIVE: To assess the utility of plasma phosphorylated tau 217 (p-tau217) for classifying Aβ status in cognitively unimpaired individuals, both as a stand-alone test and in a 2-step approach where positive plasma results were confirmed using a second modality (Aβ positron emission tomography [PET] or cerebrospinal fluid [CSF]).
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional cohort study used data collected between June 2009 and March 2024. We included 2916 cognitively unimpaired participants from 12 international independent observational cohorts in the US, Europe, Australia, and Canada with available plasma p-tau217 levels and CSF or PET Aβ biomarkers. Performance comparisons between mass spectrometry and immunoassay-based p-tau217 measurements were also performed (n = 964).
EXPOSURES: Plasma p-tau217 levels measured by immunoassay.
MAIN OUTCOME AND MEASURES: Aβ status, determined by CSF or Aβ PET biomarkers.
RESULTS: Participants had a mean (SD) age of 66.9 (9.9) years; 971 (33.3%) were Aβ positive by either CSF or PET, 1667 (57.2%) were women, and 1108 (38.1%) carried at least 1 APOE ε4 allele. As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82). In a 2-step workflow, the PPV and accuracy significantly increased to 91% (95% CI, 86-95). While this approach required screening of 677 individuals with plasma p-tau217 to identify 100 Aβ-positive individuals, compared to 536 participants when using PET alone, it reduced the need for PET testing to 124. Immunoassays demonstrated comparable PPVs to mass spectrometry (80% [95% CI, 74-86] vs 85% [95% CI, 81-90]; P = .12) but significantly lower overall accuracy (82% [95% CI, 79-84]% vs 88 [95% CI, 86-90]; P < .001) and true Aβ-positive detection rate (49% [95% CI, 43-55] vs 69% [95% CI, 64-75]; P < .001).
CONCLUSIONS AND RELEVANCE: The findings highlight the potential of plasma p-tau217 as a stand-alone test-or when used in a sequential 2-step approach alongside PET or CSF testing-as a cost-effective, scalable, and minimally burdensome strategy for identifying preclinical AD. Tailored screening workflows that incorporate p-tau217 can improve efficiency in participant selection for preclinical AD trials and, in the future, help guide access to disease-modifying treatments.