Plasma phosphorylated tau 217 and amyloid‑β 42/40 for amyloid risk in subgroups
Abstract Background Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β (Aβ) pathology. Recently, plasma biomarkers, particularly p-tau217, have emerged as promising tools for early diagnosis and risk stratification. In this retrospective study, we evaluated the diagnostic per...
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BMC
2025-08-01
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| Series: | Alzheimer’s Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13195-025-01826-3 |
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| author | Heekyoung Kang Heejin Yoo Jungah Lee Soyeon Yoon Henrik Zetterberg Kaj Blennow Fernando Gonzalez-Ortiz Nicholas J. Ashton Theresa A. Day Sung Hoon Kang Jihwan Yun Min Young Chun Eun Hye Lee Jun Pyo Kim Hee Jin Kim Duk L. Na Hyemin Jang Daeun Shin Sang Won Seo the K-ROAD study group |
| author_facet | Heekyoung Kang Heejin Yoo Jungah Lee Soyeon Yoon Henrik Zetterberg Kaj Blennow Fernando Gonzalez-Ortiz Nicholas J. Ashton Theresa A. Day Sung Hoon Kang Jihwan Yun Min Young Chun Eun Hye Lee Jun Pyo Kim Hee Jin Kim Duk L. Na Hyemin Jang Daeun Shin Sang Won Seo the K-ROAD study group |
| author_sort | Heekyoung Kang |
| collection | DOAJ |
| description | Abstract Background Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β (Aβ) pathology. Recently, plasma biomarkers, particularly p-tau217, have emerged as promising tools for early diagnosis and risk stratification. In this retrospective study, we evaluated the diagnostic performance of p-tau217 combined with other plasma biomarkers in distinguishing Aβ Positron emission tomography (PET) positivity in cognitively unimpaired (CU) and cognitively impaired (CI) individuals across diverse clinical subgroups. Methods We analyzed 2,497 participants from the Korea-Registries to Overcome dementia and Accelerate Dementia (K-ROAD) cohort, including 636 CU and 1,971 CI individuals. Plasma p-tau217 was measured using both SIngle MOlecule Array (SIMOA) and Meso Scale Discovery (MSD) assays, alongside Aβ42/40, Glial fibrillary acidic protein (GFAP), and Neurofilament light chain (NfL). We assessed the diagnostic performance of biomarker combinations for Aβ PET positivity through the area under the receiver operating characteristic curve (AUC), Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC), and performed subgroup analyses based on age, sex, body mass index (BMI), and Apolipoprotein E (APOE) ε4 status. To assess applicability, we stratified the cohort by recruitment site into a development set (Samsung Medical Center, n = 1,545) and a validation set (other centers, n = 952). Results In CU individuals from the development cohort, the combination of p-tau217 and Aβ42/40 significantly improved diagnostic accuracy (AUC: ALZpath 0.937 vs. 0.905, MSD 0.901 vs. 0.861; p < 0.05, DeLong test; 95% CIs) and model fit (AIC /BIC, p < 0.001) compared to p-tau217 alone. In contrast, in CI individuals, the combination provided only modest improvements in model fit without significantly enhancing AUC. GFAP and NfL did not contribute significantly to amyloid detection in either group. These findings were successfully validated in an independent cohort from other centers. Subgroup analyses in CU individuals showed the greatest improvements in older adults, females, and APOE4 non-carriers, regardless of obesity status. In CI individuals, the combination had no significant impact on AUC except in males, where a small but significant increase was observed (p = 0.002). Conclusion Combining p-tau217 with Aβ42/40 enhances amyloid detection in CU individuals, improving both diagnostic accuracy and model fit, whereas its impact in CI individuals is limited. These results highlight the potential of plasma biomarker combinations for refining early AD diagnostics and individualized risk assessment. |
| format | Article |
| id | doaj-art-3f14b09a553d4e758dc6725b81d62181 |
| institution | Kabale University |
| issn | 1758-9193 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | Alzheimer’s Research & Therapy |
| spelling | doaj-art-3f14b09a553d4e758dc6725b81d621812025-08-20T03:42:30ZengBMCAlzheimer’s Research & Therapy1758-91932025-08-0117111210.1186/s13195-025-01826-3Plasma phosphorylated tau 217 and amyloid‑β 42/40 for amyloid risk in subgroupsHeekyoung Kang0Heejin Yoo1Jungah Lee2Soyeon Yoon3Henrik Zetterberg4Kaj Blennow5Fernando Gonzalez-Ortiz6Nicholas J. Ashton7Theresa A. Day8Sung Hoon Kang9Jihwan Yun10Min Young Chun11Eun Hye Lee12Jun Pyo Kim13Hee Jin Kim14Duk L. Na15Hyemin Jang16Daeun Shin17Sang Won Seo18the K-ROAD study groupDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of MedicineAlzheimer’s Disease Convergence Research Center, Samsung Medical CenterAlzheimer’s Disease Convergence Research Center, Samsung Medical CenterAlzheimer’s Disease Convergence Research Center, Samsung Medical CenterDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of GothenburgEli Lilly and Company, Lilly Corporate CenterDepartment of Neurology, Korea University Guro Hospital, Korea University College of MedicineDepartment of Neurology, Soonchunhyang University Bucheon HospitalDepartment of Neurology, Yonsei University College of MedicineDepartment of Radiology and Imaging Sciences, Indiana University School of MedicineDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Neurology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of MedicineAbstract Background Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β (Aβ) pathology. Recently, plasma biomarkers, particularly p-tau217, have emerged as promising tools for early diagnosis and risk stratification. In this retrospective study, we evaluated the diagnostic performance of p-tau217 combined with other plasma biomarkers in distinguishing Aβ Positron emission tomography (PET) positivity in cognitively unimpaired (CU) and cognitively impaired (CI) individuals across diverse clinical subgroups. Methods We analyzed 2,497 participants from the Korea-Registries to Overcome dementia and Accelerate Dementia (K-ROAD) cohort, including 636 CU and 1,971 CI individuals. Plasma p-tau217 was measured using both SIngle MOlecule Array (SIMOA) and Meso Scale Discovery (MSD) assays, alongside Aβ42/40, Glial fibrillary acidic protein (GFAP), and Neurofilament light chain (NfL). We assessed the diagnostic performance of biomarker combinations for Aβ PET positivity through the area under the receiver operating characteristic curve (AUC), Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC), and performed subgroup analyses based on age, sex, body mass index (BMI), and Apolipoprotein E (APOE) ε4 status. To assess applicability, we stratified the cohort by recruitment site into a development set (Samsung Medical Center, n = 1,545) and a validation set (other centers, n = 952). Results In CU individuals from the development cohort, the combination of p-tau217 and Aβ42/40 significantly improved diagnostic accuracy (AUC: ALZpath 0.937 vs. 0.905, MSD 0.901 vs. 0.861; p < 0.05, DeLong test; 95% CIs) and model fit (AIC /BIC, p < 0.001) compared to p-tau217 alone. In contrast, in CI individuals, the combination provided only modest improvements in model fit without significantly enhancing AUC. GFAP and NfL did not contribute significantly to amyloid detection in either group. These findings were successfully validated in an independent cohort from other centers. Subgroup analyses in CU individuals showed the greatest improvements in older adults, females, and APOE4 non-carriers, regardless of obesity status. In CI individuals, the combination had no significant impact on AUC except in males, where a small but significant increase was observed (p = 0.002). Conclusion Combining p-tau217 with Aβ42/40 enhances amyloid detection in CU individuals, improving both diagnostic accuracy and model fit, whereas its impact in CI individuals is limited. These results highlight the potential of plasma biomarker combinations for refining early AD diagnostics and individualized risk assessment.https://doi.org/10.1186/s13195-025-01826-3Alzheimer’s diseasePlasma biomarkersp-tau217Aβ42/40Diagnostic accuracy |
| spellingShingle | Heekyoung Kang Heejin Yoo Jungah Lee Soyeon Yoon Henrik Zetterberg Kaj Blennow Fernando Gonzalez-Ortiz Nicholas J. Ashton Theresa A. Day Sung Hoon Kang Jihwan Yun Min Young Chun Eun Hye Lee Jun Pyo Kim Hee Jin Kim Duk L. Na Hyemin Jang Daeun Shin Sang Won Seo the K-ROAD study group Plasma phosphorylated tau 217 and amyloid‑β 42/40 for amyloid risk in subgroups Alzheimer’s Research & Therapy Alzheimer’s disease Plasma biomarkers p-tau217 Aβ42/40 Diagnostic accuracy |
| title | Plasma phosphorylated tau 217 and amyloid‑β 42/40 for amyloid risk in subgroups |
| title_full | Plasma phosphorylated tau 217 and amyloid‑β 42/40 for amyloid risk in subgroups |
| title_fullStr | Plasma phosphorylated tau 217 and amyloid‑β 42/40 for amyloid risk in subgroups |
| title_full_unstemmed | Plasma phosphorylated tau 217 and amyloid‑β 42/40 for amyloid risk in subgroups |
| title_short | Plasma phosphorylated tau 217 and amyloid‑β 42/40 for amyloid risk in subgroups |
| title_sort | plasma phosphorylated tau 217 and amyloid β 42 40 for amyloid risk in subgroups |
| topic | Alzheimer’s disease Plasma biomarkers p-tau217 Aβ42/40 Diagnostic accuracy |
| url | https://doi.org/10.1186/s13195-025-01826-3 |
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