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Journal article
Detection and staging of Alzheimer's disease by plasma pTau217 on a high throughput immunoassay platform
EBioMedicine, Vol.109, 105405
2024
PMID: 39437657
Abstract
Background
Plasma phospho-tau 217 (pTau217) assays can accurately detect Alzheimer's disease (AD) pathology, but clinical application is limited by the need for specialised equipment. This study tests the performance of a plasma pTau217 assay performed on the Lumipulse-G® platform, that is in widespread clinical use, for selecting patients for therapy based on β-amyloid (Aβ) status and tau staging.
Methods
Participants included 388 individuals with 18F-NAV4694 Aβ-PET and 18F-MK6240 tau-PET. Association of pTau217 with PET was examined using Spearman's correlation. Discriminative performance for Aβ and tau PET status as well as tau staging was assessed using Receiver Operating Characteristic analysis.
Findings
Plasma pTau217 had a high correlation with both Aβ Centiloid (r = 0.76) and tau SUVRmeta-temporal (r = 0.78). Area under curve (AUC) was 0.93 for Aβ− vs Aβ+ and 0.94 for tau− vs tau+. Applying one threshold (Youden's index), pTau217 was 87% accurate in classification of participants to Aβ− vs Aβ+. Applying two thresholds to classify participants into Low, Indeterminate, and High zones, 17.8% had Indeterminate results and among Low/High zone participants, 92% were correctly classified as Aβ− or Aβ+. The assay accurately discriminated moderate/high neocortical tau from no tau or tau limited to mesial-temporal lobe (AUC 0.97) and high neocortical tau from all others (AUC 0.94).
Interpretation
Plasma pTau217, measured by the widely-available, fully-automated Lumipulse®, was a strong predictor of both Aβ and tau PET status and demonstrated strong predictive power in identifying individuals likely to benefit the most from anti-Aβ treatments.
Funding
NHMRC grants 1132604, 1140853, 1152623 and AbbVie.
Details
- Title
- Detection and staging of Alzheimer's disease by plasma pTau217 on a high throughput immunoassay platform
- Authors/Creators
- Azadeh Feizpour - Florey Institute of Neuroscience and Mental HealthJames David Doecke - Australian e-Health Research CentreVincent Doré - Australian e-Health Research CentreNatasha Krishnadas - Austin HealthKun Huang - Austin HealthPierrick Bourgeat - Commonwealth Scientific and Industrial Research OrganisationSimon Matthew Laws - Edith Cowan UniversityChristopher Fowler - The University of MelbourneJoanne Robertson - Florey Institute of Neuroscience and Mental HealthLucy Mackintosh - Florey Institute of Neuroscience and Mental HealthScott Ayton - Florey Institute of Neuroscience and Mental HealthRalph Martins - Australian Alzheimer's Research Foundation, Nedlands, Perth, AustraliaStephanie Ruth Rainey-Smith - Murdoch University, Centre for Healthy AgeingKevin Taddei - Australian Alzheimer’s Research FoundationLarry Ward - Florey Institute of Neuroscience and Mental HealthEddie Stage - AbbVie (United States)Anthony Wilson Bannon - AbbVie (United States)Colin Louis Masters - Florey Institute of Neuroscience and Mental HealthJurgen Fripp - CSIRO Health and BiosecurityVictor Luis Villemagne - Mental Health Research InstituteChristopher Cleon Rowe - Austin Health
- Publication Details
- EBioMedicine, Vol.109, 105405
- Publisher
- Elsevier B.V.
- Grant note
- 1132604; 1140853; 1152623 / NHMRC (https://doi.org/10.13039/501100000925) AbbVie (https://doi.org/10.13039/100006483)
- Identifiers
- 991005707252907891
- Copyright
- © 2024 The Authors.
- Murdoch Affiliation
- Centre for Healthy Ageing
- Language
- English
- Resource Type
- Journal article
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