| Title: |
Detection and staging of Alzheimer's disease by plasma pTau217 on a high throughput immunoassay platform |
| Authors: |
Feizpour, A; Doecke, JD; Doré, V; Krishnadas, N; Huang, K; Bourgeat, P; Laws, SM; Fowler, C; Robertson, J; Mackintosh, L; Ayton, S; Martins, R; Rainey-Smith, SR; Taddei, K; Ward, L; Stage, E; Bannon, AW; Masters, CL; Fripp, J; Villemagne, VL; Rowe, CC |
| Publisher Information: |
ELSEVIER |
| Publication Year: |
2024 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2352-3964 |
| Relation: |
NHMRC/1152623; https://hdl.handle.net/11343/359022 |
| Availability: |
https://hdl.handle.net/11343/359022 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.CCEC17B8 |
| Database: |
BASE |