Plasma phospho-tau217 as a predictive biomarker for Alzheimer’s disease in a large south American cohort
Abstract Background Blood-based Alzheimer’s disease (AD) biomarkers have been increasingly employed for diagnostic, prognostic, and therapeutic monitoring purposes, due to accuracy in distinguishing AD pathophysiologic process. Compared to other p-tau isoforms, plasma p-tau217 exhibits stronger asso...
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BMC
2025-01-01
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| Series: | Alzheimer’s Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13195-024-01655-w |
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| author | Neetesh Pandey Zikun Yang Basilio Cieza Dolly Reyes-Dumeyer Min Suk Kang Rosa Montesinos Marcio Soto-Añari Nilton Custodio Lawrence S. Honig Giuseppe Tosto |
| author_facet | Neetesh Pandey Zikun Yang Basilio Cieza Dolly Reyes-Dumeyer Min Suk Kang Rosa Montesinos Marcio Soto-Añari Nilton Custodio Lawrence S. Honig Giuseppe Tosto |
| author_sort | Neetesh Pandey |
| collection | DOAJ |
| description | Abstract Background Blood-based Alzheimer’s disease (AD) biomarkers have been increasingly employed for diagnostic, prognostic, and therapeutic monitoring purposes, due to accuracy in distinguishing AD pathophysiologic process. Compared to other p-tau isoforms, plasma p-tau217 exhibits stronger associations with AD hallmarks in CSF and brain. However, most studies have been conducted in non-Hispanic Whites, limiting our understanding of the performances and utility of these biomarkers across ethnicities. Methods We examined a cohort of Peruvians from the GAPP study, a recently established cohort of Peruvian mestizos from Lima and indigenous groups from Southern Peru (Aymaras and Quechuas). We tested plasma levels of p-tau using the Quanterix Simoa ALZpathp-tau217 assay in 525 samples and tested the association between p-tau217 and clinical diagnosis (healthy controls n = 234 vs. AD n = 113) using generalized mixed regression models, adjusting for sex, age, education, APOE-e4 allele (fixed effects) and study site (random effect). We also tested biomarker levels in MCI (n = 178) vs. other groups. The receiver operating characteristics area under the curve (ROC-AUC) was used to evaluate the biomarker’s classification performances. Result Participants showed on average 80% Native American ancestry. p-tau217 was significantly associated with AD (β = 2.61, 95%CI = 0.61–4.29) and its levels were inversely correlated with cognitive performances; p-tau217 levels did not differ between controls and MCI (p-value > 0.05). p-tau217 levels were higher in participants carrying at least one APOE-e4 allele (OR = 2.31, 95%CI = 1.85–2.90). The ROC-AUC for p-tau217 was estimated at 82.82% in the fully adjusted model. Conclusion To our knowledge, this is the largest study conducted in a South American cohort phenotyped for AD with available p-tau217. Most investigations have previously focused on highly selected cohorts with established AD-endophenotypes (CSF biomarkers, autopsy report, PET etc.), while data on cohorts with clinical assessment are currently lacking, especially in non-European populations. |
| format | Article |
| id | doaj-art-8305edb2ee894a7d8067dccce09fef69 |
| institution | DOAJ |
| issn | 1758-9193 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Alzheimer’s Research & Therapy |
| spelling | doaj-art-8305edb2ee894a7d8067dccce09fef692025-08-20T02:53:57ZengBMCAlzheimer’s Research & Therapy1758-91932025-01-011711810.1186/s13195-024-01655-wPlasma phospho-tau217 as a predictive biomarker for Alzheimer’s disease in a large south American cohortNeetesh Pandey0Zikun Yang1Basilio Cieza2Dolly Reyes-Dumeyer3Min Suk Kang4Rosa Montesinos5Marcio Soto-Añari6Nilton Custodio7Lawrence S. Honig8Giuseppe Tosto9Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia UniversityTaub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia UniversityTaub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia UniversityTaub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia UniversityTaub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia UniversityUnidad de diagnóstico de deterioro cognitivo y prevención de demencia, Instituto Peruano de NeurocienciasUniversidad Católica San PabloUnidad de diagnóstico de deterioro cognitivo y prevención de demencia, Instituto Peruano de NeurocienciasTaub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia UniversityTaub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia UniversityAbstract Background Blood-based Alzheimer’s disease (AD) biomarkers have been increasingly employed for diagnostic, prognostic, and therapeutic monitoring purposes, due to accuracy in distinguishing AD pathophysiologic process. Compared to other p-tau isoforms, plasma p-tau217 exhibits stronger associations with AD hallmarks in CSF and brain. However, most studies have been conducted in non-Hispanic Whites, limiting our understanding of the performances and utility of these biomarkers across ethnicities. Methods We examined a cohort of Peruvians from the GAPP study, a recently established cohort of Peruvian mestizos from Lima and indigenous groups from Southern Peru (Aymaras and Quechuas). We tested plasma levels of p-tau using the Quanterix Simoa ALZpathp-tau217 assay in 525 samples and tested the association between p-tau217 and clinical diagnosis (healthy controls n = 234 vs. AD n = 113) using generalized mixed regression models, adjusting for sex, age, education, APOE-e4 allele (fixed effects) and study site (random effect). We also tested biomarker levels in MCI (n = 178) vs. other groups. The receiver operating characteristics area under the curve (ROC-AUC) was used to evaluate the biomarker’s classification performances. Result Participants showed on average 80% Native American ancestry. p-tau217 was significantly associated with AD (β = 2.61, 95%CI = 0.61–4.29) and its levels were inversely correlated with cognitive performances; p-tau217 levels did not differ between controls and MCI (p-value > 0.05). p-tau217 levels were higher in participants carrying at least one APOE-e4 allele (OR = 2.31, 95%CI = 1.85–2.90). The ROC-AUC for p-tau217 was estimated at 82.82% in the fully adjusted model. Conclusion To our knowledge, this is the largest study conducted in a South American cohort phenotyped for AD with available p-tau217. Most investigations have previously focused on highly selected cohorts with established AD-endophenotypes (CSF biomarkers, autopsy report, PET etc.), while data on cohorts with clinical assessment are currently lacking, especially in non-European populations.https://doi.org/10.1186/s13195-024-01655-wAlzheimer’s diseasePlasma biomarkerP-tau217PlasmaAPOE |
| spellingShingle | Neetesh Pandey Zikun Yang Basilio Cieza Dolly Reyes-Dumeyer Min Suk Kang Rosa Montesinos Marcio Soto-Añari Nilton Custodio Lawrence S. Honig Giuseppe Tosto Plasma phospho-tau217 as a predictive biomarker for Alzheimer’s disease in a large south American cohort Alzheimer’s Research & Therapy Alzheimer’s disease Plasma biomarker P-tau217 Plasma APOE |
| title | Plasma phospho-tau217 as a predictive biomarker for Alzheimer’s disease in a large south American cohort |
| title_full | Plasma phospho-tau217 as a predictive biomarker for Alzheimer’s disease in a large south American cohort |
| title_fullStr | Plasma phospho-tau217 as a predictive biomarker for Alzheimer’s disease in a large south American cohort |
| title_full_unstemmed | Plasma phospho-tau217 as a predictive biomarker for Alzheimer’s disease in a large south American cohort |
| title_short | Plasma phospho-tau217 as a predictive biomarker for Alzheimer’s disease in a large south American cohort |
| title_sort | plasma phospho tau217 as a predictive biomarker for alzheimer s disease in a large south american cohort |
| topic | Alzheimer’s disease Plasma biomarker P-tau217 Plasma APOE |
| url | https://doi.org/10.1186/s13195-024-01655-w |
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