@article{10902/36080,
year = {2024},
url = {https://hdl.handle.net/10902/36080},
abstract = {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.},
organization = {Funding: No funding has been received for this study. Acknowledgements: We would like to thank the participants of the Valdecilla Cohort for their selfless help and collaboration with research in neurodegenerative diseases. We want to particulary acknowledge the patients and the Biobank Valdecilla (PT20/00067) integrated in the Spanish Biobank Network for its collaboration.},
publisher = {Springer Nature},
publisher = {Alzheimer's Research & Therapy, 2024, 16, 268},
title = {Longitudinal trajectory of plasma p-tau217 in cognitively unimpaired subjects},
author = {Martínez Dubarbie, Francisco and Guerra Ruiz, Armando Raúl and López García, Sara and Lage Martínez, Carmen and Fernández Matarrubia, Marta and Pozueta Cantudo, Ana and García-Martínez, María and Corrales Pardo, Andrea and Bravo González, María Paz and López Hoyos, Marcos and Irure Ventura, Juan and Marco de Lucas, Enrique and Drake Pérez, Marta and García Unzueta, María Teresa and Sánchez Juan, Pascual and Rodríguez Rodríguez, Eloy Manuel},
}