Detection and staging of Alzheimer's disease by plasma pTau217 on a high throughput immunoassay platformResearch in context
Azadeh Feizpour,
James David Doecke,
Vincent Doré,
Natasha Krishnadas,
Kun Huang,
Pierrick Bourgeat,
Simon Matthew Laws,
Christopher Fowler,
Joanne Robertson,
Lucy Mackintosh,
Scott Ayton,
Ralph Martins,
Stephanie Ruth Rainey-Smith,
Kevin Taddei,
Larry Ward,
Eddie Stage,
Anthony Wilson Bannon,
Colin Louis Masters,
Jurgen Fripp,
Victor Luis Villemagne,
Christopher Cleon Rowe
Affiliations
Azadeh Feizpour
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Victoria, Australia
James David Doecke
The Australian e-Health Research Centre, CSIRO, Brisbane, Queensland, Australia; Centre for Precision Health, Edith Cowan University, Joondalup, Western Australia, Australia
Vincent Doré
Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Victoria, Australia; The Australian e-Health Research Centre, CSIRO, Melbourne, Victoria, Australia
Natasha Krishnadas
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Victoria, Australia
Kun Huang
Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Victoria, Australia
Pierrick Bourgeat
The Australian e-Health Research Centre, CSIRO, Brisbane, Queensland, Australia
Simon Matthew Laws
Centre for Precision Health, Edith Cowan University, Joondalup, Western Australia, Australia; Collaborative Genomics and Translation Group, Edith Cowan University, Joondalup, Western Australia, Australia; Curtin Medical School, Curtin University, Bentley, Western Australia, Australia
Christopher Fowler
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia
Joanne Robertson
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia
Lucy Mackintosh
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia
Scott Ayton
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia
Ralph Martins
Australian Alzheimer's Research Foundation, Nedlands, Perth, Australia
Stephanie Ruth Rainey-Smith
Australian Alzheimer's Research Foundation, Nedlands, Perth, Australia; Centre for Healthy Ageing, Health Futures Institute, Murdoch University, Murdoch, Western Australia, Australia
Kevin Taddei
Australian Alzheimer's Research Foundation, Nedlands, Perth, Australia
Larry Ward
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia
Eddie Stage
AbbVie, North Chicago, IL, USA
Anthony Wilson Bannon
AbbVie, North Chicago, IL, USA
Colin Louis Masters
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia
Jurgen Fripp
The Australian e-Health Research Centre, CSIRO, Brisbane, Queensland, Australia
Victor Luis Villemagne
Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Victoria, Australia; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
Christopher Cleon Rowe
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Victoria, Australia; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Corresponding author. Department of Molecular Imaging & Therapy, Austin Health, 145 Studley Road, Heidelberg, Victoria, 3084, Australia.
Summary: 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.
