Longitudinal trajectory of plasma p-tau217 in cognitively unimpaired subjects
Background: The advent of Alzheimer's disease-modifying drugs requires accurate biological diagnosis to identify candidates for these therapies. So far, the most promising single plasma biomarker is phosphorylated tau at threonine 217 (p-tau217). To understand its biological features, it is ess...
| Autores: | , , , , , , , , , , , , , , , |
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| Tipo de documento: | artigo |
| Data de publicação: | 2024 |
| País: | España |
| Recursos: | Universidad de Cantabria (UC) |
| Repositório: | UCrea Repositorio Abierto de la Universidad de Cantabria |
| Idioma: | inglês |
| OAI Identifier: | oai:repositorio.unican.es:10902/36080 |
| Acesso em linha: | https://hdl.handle.net/10902/36080 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Plasma p-tau217 Alzheimer’s disease Early diagnosis Longitudinal Healthy controls Biomarkers |
| Resumo: | Background: The advent of Alzheimer's disease-modifying drugs requires accurate biological diagnosis to identify candidates for these therapies. So far, the most promising single plasma biomarker is phosphorylated tau at threonine 217 (p-tau217). To understand its biological features, it is essential to know its longitudinal trajectory and factors influencing it in cognitively unimpaired subjects with no brain pathology. Methods: We analyzed longitudinal plasma p-tau217 values (mean follow-up time = 768.3 days) in a cohort of 209 healthy volunteers. We have studied factors associated with plasma p-tau217 changes by using different linear mixed-effects models. Results: In amyloid-negative cognitively healthy subjects (n = 151) carriers of ApoE epsilon4 allele had significantly higher p-tau217 values than non-carriers (0.85 pg/mL; p-value < 0.001) and also a greater rate of change (0.01 pg/mL/year; p-value < 0.001). In the overall sample, including subjects with amyloid and tau pathology we have seen that amyloid positive subjects had higher predicted baseline plasma p-tau217 values than amyloid negative subjects (0.16 pg/mL; p-value < 0.001) and a greater rate of change (0.00004 pg/mL/day; p-value < 0.001). Subjects considered tau positive also showed a greater rate of change of p-tau217 with respect to tau negative (0.00005 pg/mL/day; p-value < 0.001). A + T + N + participants showed a higher baseline p-tau217 levels than A-T-N- subjects (0.2 pg/mL; p-value < 0.001) and also a greater rate of change (0.00006 pg/mL/day; p-value = 0.002). ApoE epsilon4 carriers had a greater rate of change than non-carriers (0.00003 pg/mL/day; p-value = 0.03). Conclusion: In amyloid-negative cognitively unimpaired subjects, ApoE4 status influenced both baseline levels and rate of change of plasma p-tau217. Other factors such as age, sex or glomerular filtration rate have not shown significant influence on plasma p-tau217 levels in this group. |
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