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Combining Lumipulse p-tau217 and Aβ42/40 as confirmatory tests for Aβ positivity prior to disease-modifying therapy
Journal article   Open access   Peer reviewed

Combining Lumipulse p-tau217 and Aβ42/40 as confirmatory tests for Aβ positivity prior to disease-modifying therapy

James D Doecke, Ahmed Chenna, Mintzu Lo, Youssouf Badal, Brandon Yee, Robert Martone, Christos Petropoulos, Christopher J Fowler, Simon Laws, Stephanie R Rainey-Smith, …
Alzheimer's & dementia, Vol.21(9), e70707
2025
DOI: https://doi.org/10.1002/alz.70707
PMID: 40976838
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Published2.67 MBDownloadView
CC BY-NC-ND V4.0,  Open Access

Abstract

Alzheimer's disease Centiloid amyloid beta cognitively unimpaired plasma biomarker prediction
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.

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