Measuring pTau217 seems to be a perfect tool for Prof. Masters when he starts (???) a new PBT2 study. He has a PBT2 license from ATH. This a new paper from the Florey Institute.

Full paper: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00441-9/fulltext

EBioMedicine

. 2024 Oct 21:109:105405.

doi: 10.1016/j.ebiom.2024.105405. Online ahead of print.

Detection and staging of Alzheimer's disease by plasma pTau217 on a high throughput immunoassay platform

Azadeh Feizpour ¹, James David Doecke ², Vincent Doré ³, Natasha Krishnadas ¹, Kun Huang ⁴, Pierrick Bourgeat ⁵, Simon Matthew Laws ⁶, Christopher Fowler ⁷, Joanne Robertson ⁷, Lucy Mackintosh ⁷, Scott Ayton ⁷, Ralph Martins ⁸, Stephanie Ruth Rainey-Smith ⁹, Kevin Taddei ⁸, Larry Ward ⁷, Eddie Stage ¹⁰, Anthony Wilson Bannon ¹⁰, Colin Louis Masters ⁷, Jurgen Fripp ⁵, Victor Luis Villemagne ¹¹, Christopher Cleon Rowe ¹²

Affiliations Expand

• PMID: 39437657

DOI: 10.1016/j.ebiom.2024.105405

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 SUVR_{meta-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.