{"id":"doi:10.1038/s43587-024-00731-y","kind":"article","title":"Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability","authors":["Therriault J","Janelidze S","Benedet AL","Ashton NJ","Arranz Martínez J","Gonzalez-Escalante A","Bellaver B","Alcolea D","Vrillon A","Karim H","Mielke MM","Hyung Hong C","Roh HW","Contador J","Puig Pijoan A","Algeciras-Schimnich A","Vemuri P","Graff-Radford J","Lowe VJ","Karikari TK","Jonaitis E","Brum W","Tissot C","Servaes S","Rahmouni N"],"author_count":56,"year":2024,"published":"2024-11-12","venue":"Nature aging","cited_by":103,"doi":"10.1038/s43587-024-00731-y","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s43587-024-00731-y","archive_url":"https://space-kitty.com/papers/doi:10.1038/s43587-024-00731-y","updated":null,"pmid":"39533113","pmcid":"PMC11564087","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC11564087/pdf","abstract":"Recently approved anti-amyloid immunotherapies for Alzheimer's disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need for PET or CSF testing; however, their interpretation at the individual level and the circumstances requiring confirmatory testing are poorly understood. Individual-level interpretation of diagnostic test results requires knowledge of disease prevalence in relation to clinical presentation (clinical pretest probability). Here, in a study of 6,896 individuals evaluated from 11 cohort studies from six countries, we determined the positive and negative predictive value of five plasma biomarkers for amyloid-β pathology in cognitively impaired individuals in relation to clinical pretest probability. We observed that p-tau217 could rule in amyloid-β pathology in individuals with probable AD dementia (positive predictive value above 95%). In mild cognitive impairment, p-tau217 interpretation depended on patient age. Negative p-tau217 results could rule out amyloid-β pathology in individuals with non-AD dementia syndromes (negative predictive value between 90% and 99%). Our findings provide a framework for the individual-level interpretation of plasma biomarkers, suggesting that p-tau217 combined with clinical phenotyping can identify patients where amyloid-β pathology can be ruled in or out without the need for PET or CSF confirmatory testing.","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 \"Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability\" by Therriault J, Janelidze S, Benedet AL et al., https://doi.org/10.1038/s43587-024-00731-y, 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":[]}