Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability

Therriault, Joseph; González Escalante, Armand; Contador, Jose; Puig Pijoan, Albert; Suárez-Calvet, Marc; Rosa-Neto, Pedro

doi:http://dx.doi.org/10.1038/s43587-024-00731-y

Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability

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Therriault J, Janelidze S, Benedet AL, et al. Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability. Nature Aging. 2024;4(11):1529-37. DOI: 10.1038/s43587-024-00731-y

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.