{"id":"doi:10.1038/s43587-023-00471-5","kind":"article","title":"A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases","authors":["Brum WS","Cullen NC","Janelidze S","Ashton NJ","Zimmer ER","Therriault J","Benedet AL","Rahmouni N","Tissot C","Stevenson J","Servaes S","Triana-Baltzer G","Kolb HC","Palmqvist S","Stomrud E","Rosa-Neto P","Blennow K","Hansson O"],"author_count":18,"year":2023,"published":"2023-08-31","venue":"Nature aging","cited_by":233,"doi":"10.1038/s43587-023-00471-5","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s43587-023-00471-5","archive_url":"https://space-kitty.com/papers/doi:10.1038/s43587-023-00471-5","updated":null,"pmid":"37653254","pmcid":"PMC10501903","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC10501903/pdf","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.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases\" by Brum WS, Cullen NC, Janelidze S et al., https://doi.org/10.1038/s43587-023-00471-5, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"neurodegeneration","name":"Alzheimer's, Parkinson's & Neurodegeneration","domain_slug":"medicine"}],"cited_in_dossiers":[]}