학술논문
A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases
Document Type
Original Paper
Author
Brum, Wagner S.; Cullen, Nicholas C.; Janelidze, Shorena; Ashton, Nicholas J.; Zimmer, Eduardo R.; Therriault, Joseph; Benedet, Andrea L.; Rahmouni, Nesrine; Tissot, Cécile; Stevenson, Jenna; Servaes, Stijn; Triana-Baltzer, Gallen; Kolb, Hartmuth C.; Palmqvist, Sebastian; Stomrud, Erik; Rosa-Neto, Pedro; Blennow, Kaj; Hansson, Oskar
Source
Nature Aging. 3(9):1079-1090
Subject
Language
English
ISSN
2662-8465
Abstract
Cost-effective strategies for identifying amyloid-β (Aβ) positivity in patients with cognitive impairment are urgently needed with recent approvals of anti-Aβ immunotherapies for Alzheimer’s disease (AD). Blood biomarkers can accurately detect AD pathology, but it is unclear whether their incorporation into a full diagnostic workflow can reduce the number of confirmatory cerebrospinal fluid (CSF) or positron emission tomography (PET) tests needed while accurately classifying patients. We evaluated a two-step workflow for determining Aβ-PET status in patients with mild cognitive impairment (MCI) from two independent memory clinic-based cohorts (n = 348). A blood-based model including plasma tau protein 217 (p-tau217), age and APOE ε4 status was developed in BioFINDER-1 (area under the curve (AUC) = 89.3%) and validated in BioFINDER-2 (AUC = 94.3%). In step 1, the blood-based model was used to stratify the patients into low, intermediate or high risk of Aβ-PET positivity. In step 2, we assumed referral only of intermediate-risk patients to CSF Aβ42/Aβ40 testing, whereas step 1 alone determined Aβ-status for low- and high-risk groups. Depending on whether lenient, moderate or stringent thresholds were used in step 1, the two-step workflow overall accuracy for detecting Aβ-PET status was 88.2%, 90.5% and 92.0%, respectively, while reducing the number of necessary CSF tests by 85.9%, 72.7% and 61.2%, respectively. In secondary analyses, an adapted version of the BioFINDER-1 model led to successful validation of the two-step workflow with a different plasma p-tau217 immunoassay in patients with cognitive impairment from the TRIAD cohort (n = 84). In conclusion, using a plasma p-tau217-based model for risk stratification of patients with MCI can substantially reduce the need for confirmatory testing while accurately classifying patients, offering a cost-effective strategy to detect AD in memory clinic settings.
Risk stratification based on plasma p-tau217 can substantially reduce the need for invasive or expensive testing when screening for Aβ positivity in patients with cognitive impairment, offering a cost-effective strategy to support an Alzheimer’s disease diagnosis.
Risk stratification based on plasma p-tau217 can substantially reduce the need for invasive or expensive testing when screening for Aβ positivity in patients with cognitive impairment, offering a cost-effective strategy to support an Alzheimer’s disease diagnosis.