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

Article · 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 and 31 more

- Archive id: doi:10.1038/s43587-024-00731-y
- Published: 2024-11-12
- Venue: Nature aging
- DOI: https://doi.org/10.1038/s43587-024-00731-y
- PMID: 39533113
- PMCID: PMC11564087
- Citations: 103
- Source URL: https://doi.org/10.1038/s43587-024-00731-y
- PDF: https://europepmc.org/articles/PMC11564087/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Alzheimer's, Parkinson's & Neurodegeneration](https://space-kitty.com/topics/neurodegeneration)

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