Author Identifier (ORCID)
James D. Doecke: https://orcid.org/0000-0003-2863-0293
Simon Laws: https://orcid.org/0000-0002-4355-7082
Stephanie R. Rainey-Smith: https://orcid.org/0000-0001-7328-9624
Ralph N. Martins: https://orcid.org/0000-0002-4828-9363
Abstract
Introduction: For a blood-based biomarker to be considered a confirmatory test for the detection of abnormal amyloid beta (Aβ) levels, the sensitivity and specificity must be equivalent to that of current cerebrospinal fluid tests. Methods: In the current study we assessed the ability of phosphorylated tau (p-tau)217 and Aβ42/40 from the Lumipulse G p-tau217 and β-amyloid ratio (1-42/1-40) tests, individually and combined, to predict Aβ positron emission tomography status in two sub-cohorts from the Australian Imaging, Biomarkers, and Lifestyle Study of Ageing. Results: Testing an Alzheimer's disease continuum cohort, the area under the curve (AUC), sensitivity, specificity, and accuracy for the p-tau217/Aβ42 ratio reached 0.961, 93%, 92%, and 93%, respectively. Validation in an intention-to-treat cohort demonstrated similar AUC (0.959), with increased sensitivity (99%), decreased specificity (87%), and increased accuracy (95%). Dual cut-offs generating balanced 95% sensitivity/specificity result in 93% accuracy. Discussion: Combinations of plasma p-tau217 and Aβ42 demonstrate recommended performance, confirming the presence of Aβ positivity prior to selection for disease-modifying therapies. Highlights: The phosphorylated tau (p-tau)217/amyloid beta (Aβ)42 ratio had high performance to detect Aβ positron emission tomography (PET) status, with > 90% sensitivity, specificity, and accuracy. p-tau217/Aβ42 ratio dual cut-offs set at 95% sensitivity and specificity found 10% to 15% of participants in the intermediate zone. Cut-offs derived for the intention-to-treat cohort meet confirmatory assay criteria for a disease-modifying therapy and can be used in clinical settings.
Document Type
Journal Article
Date of Publication
9-1-2025
Volume
21
Issue
9
PubMed ID
40976838
Publication Title
Alzheimer's and Dementia
Publisher
Wiley
School
Centre for Precision Health / School of Medical and Health Sciences
Funders
Commonwealth Scientific and Industrial Research Organisation (CSIRO) / National Health and Medical Research Council / AIBL Researchers / Labcorp
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comments
Doecke, J. D., Chenna, A., Lo, M., Badal, Y., Yee, B., Martone, R., Petropoulos, C., Fowler, C. J., Laws, S., Rainey-Smith, S. R., Martins, R. N., Rowe, C. C., Masters, C. L., & Winslow, J. (2025). Combining Lumipulse p-tau217 and Aβ42/40 as confirmatory tests for Aβ positivity prior to disease-modifying therapy. Alzheimer’s and Dementia, 21(9), e70707. https://doi.org/10.1002/alz.70707