Author Identifier
James D. Doecke: https://orcid.org/0000-0003-2863-0293
Simon M. Laws: https://orcid.org/0000-0002-4355-7082
Document Type
Journal Article
Publication Title
Communications Medicine
Volume
5
Issue
1
Publisher
Nature
School
Centre for Precision Health
Publication Unique Identifier
10.1038/s43856-025-00768-z
RAS ID
78474
Funders
National Health and Medical Research Council / Enigma Australia
Grant Number
NHMRC Numbers : APP1132604, APP1140853, APP1152623
Abstract
Background: Plasma phospho-tau biomarkers, such as p217+tau, excel at identifying Alzheimer’s disease (AD) neuropathology. However, their ability to substitute for tau PET to identify AD biological stage is unclear. Methods: Participants included 248 cognitively unimpaired (CU) and 227 cognitively impaired (CI) individuals, with Janssen plasma p217+tau Simoa® assay, 18F-NAV4694 Aβ-PET (A) and 18F-MK6240 tau-PET (T) data. Biological PET stages were defined according to the Revised Criteria for Diagnosis and Staging of Alzheimer’s Disease (2024): Initial (A + T-), Early (A + TMTL +), Intermediate (A + TMOD +), and Advanced (A + THIGH +). The threshold for A+ was 25 Centiloid and for THIGH +, the 75th percentile SUVRtemporo-parietal in A + CI. Sixty percent were A +, 36% Intermediate/Advanced, and 9% Advanced. The performance of p217+tau in discriminating AD stages was assessed using Receiver Operating Characteristic (ROC) analysis and logistic regression. Results: Plasma p217+tau concentrations increase across the AD biological PET stages, except between Initial and Early stages. Screening for all AD stages (vs. A-T-), combined Intermediate/Advanced stages, or Advanced stage yields AUC of 0.92, 0.92, and 0.91, respectively (CI only: AUC 0.93, 0.89, 0.83). Plasma p217+tau Youden threshold provides sensitivity of 0.77 [0.73–0.90], specificity 0.91 [0.80–0.95], PPV 0.84 [0.71–0.89], and NPV 0.88 [0.85–0.93] for combined Intermediate/Advanced stages. For the Advanced stage alone, sensitivity is 0.89 [0.79–0.97], specificity 0.82 [0.75–0.9], NPV 0.99 [0.98–1.0], but PPV is only 0.33 [0.25–0.47]. Conclusions: In addition to accurately screening for A+ individuals, plasma p217+tau is useful for identifying a combined Intermediate/Advanced stage AD cohort or pre-screening to reduce the tau-PET required to identify Advanced stage AD individuals.
DOI
10.1038/s43856-025-00768-z
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Feizpour, A., Doré, V., Krishnadas, N., Bourgeat, P., Doecke, J. D., Saad, Z. S., ... & Rowe, C. C. (2025). Alzheimer’s disease biological PET staging using plasma p217+ tau. Communications Medicine, 5(1), 53. https://doi.org/10.1038/s43856-025-00768-z