Alzheimer’s disease biological PET staging using plasma p217+tau
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 cognit...
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Nature Portfolio
2025-02-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00768-z |
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| author | Azadeh Feizpour Vincent Doré Natasha Krishnadas Pierrick Bourgeat James D. Doecke Ziad S. Saad Gallen Triana-Baltzer Simon M. Laws Rosita Shishegar Kun Huang Christopher Fowler Larry Ward Colin L. Masters Jurgen Fripp Hartmuth C. Kolb Victor L. Villemagne Christopher C. Rowe |
| author_facet | Azadeh Feizpour Vincent Doré Natasha Krishnadas Pierrick Bourgeat James D. Doecke Ziad S. Saad Gallen Triana-Baltzer Simon M. Laws Rosita Shishegar Kun Huang Christopher Fowler Larry Ward Colin L. Masters Jurgen Fripp Hartmuth C. Kolb Victor L. Villemagne Christopher C. Rowe |
| author_sort | Azadeh Feizpour |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5524eda9126c4dd39c4b9f4bdbda2ece |
| institution | DOAJ |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| series | Communications Medicine |
| spelling | doaj-art-5524eda9126c4dd39c4b9f4bdbda2ece2025-08-20T02:54:37ZengNature PortfolioCommunications Medicine2730-664X2025-02-01511810.1038/s43856-025-00768-zAlzheimer’s disease biological PET staging using plasma p217+tauAzadeh Feizpour0Vincent Doré1Natasha Krishnadas2Pierrick Bourgeat3James D. Doecke4Ziad S. Saad5Gallen Triana-Baltzer6Simon M. Laws7Rosita Shishegar8Kun Huang9Christopher Fowler10Larry Ward11Colin L. Masters12Jurgen Fripp13Hartmuth C. Kolb14Victor L. Villemagne15Christopher C. Rowe16Florey Institute of Neuroscience and Mental HealthDepartment of Molecular Imaging & Therapy, Austin HealthFlorey Institute of Neuroscience and Mental HealthThe Australian e-Health Research Centre, CSIROThe Australian e-Health Research Centre, CSIRONeuroscience Biomarkers, Janssen Research and DevelopmentNeuroscience Biomarkers, Janssen Research and DevelopmentCentre for Precision Health, Edith Cowan UniversityThe Australian e-Health Research Centre, CSIRODepartment of Molecular Imaging & Therapy, Austin HealthFlorey Institute of Neuroscience and Mental HealthFlorey Institute of Neuroscience and Mental HealthFlorey Institute of Neuroscience and Mental HealthThe Australian e-Health Research Centre, CSIRONeuroscience Biomarkers, Janssen Research and DevelopmentDepartment of Molecular Imaging & Therapy, Austin HealthFlorey Institute of Neuroscience and Mental HealthAbstract 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.https://doi.org/10.1038/s43856-025-00768-z |
| spellingShingle | Azadeh Feizpour Vincent Doré Natasha Krishnadas Pierrick Bourgeat James D. Doecke Ziad S. Saad Gallen Triana-Baltzer Simon M. Laws Rosita Shishegar Kun Huang Christopher Fowler Larry Ward Colin L. Masters Jurgen Fripp Hartmuth C. Kolb Victor L. Villemagne Christopher C. Rowe Alzheimer’s disease biological PET staging using plasma p217+tau Communications Medicine |
| title | Alzheimer’s disease biological PET staging using plasma p217+tau |
| title_full | Alzheimer’s disease biological PET staging using plasma p217+tau |
| title_fullStr | Alzheimer’s disease biological PET staging using plasma p217+tau |
| title_full_unstemmed | Alzheimer’s disease biological PET staging using plasma p217+tau |
| title_short | Alzheimer’s disease biological PET staging using plasma p217+tau |
| title_sort | alzheimer s disease biological pet staging using plasma p217 tau |
| url | https://doi.org/10.1038/s43856-025-00768-z |
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