Longitudinal trajectory of plasma p-tau217 in cognitively unimpaired subjects

• Published in: Alzheimer's research & therapy Vol. 16; no. 1; pp. 268 - 11
• Main Authors: Martínez-Dubarbie, Francisco, Guerra-Ruiz, Armando, López-García, Sara, Lage, Carmen, Fernández-Matarrubia, Marta, Pozueta-Cantudo, Ana, García-Martínez, María, Corrales-Pardo, Andrea, Bravo, María, López-Hoyos, Marcos, Irure-Ventura, Juan, de Lucas, Enrique Marco, Drake-Pérez, Marta, García-Unzueta, María Teresa, Sánchez-Juan, Pascual, Rodríguez-Rodríguez, Eloy
• Format: Journal Article
• Language: English
• Published: London BioMed Central 20.12.2024; BioMed Central Ltd; BMC
• Subjects: Adult; Aged; Alzheimer's disease; Analysis; Apolipoprotein E4 - blood; Apolipoprotein E4 - genetics; Apolipoproteins; Biological markers; Biomarkers; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; Care and treatment; Cognition - physiology; Cohort Studies; Diagnosis; Early diagnosis; Female; Geriatric Psychiatry; Geriatrics/Gerontology; Healthy controls; Humans; Longitudinal; Longitudinal Studies; Male; Middle Aged; Neurology; Neurosciences; PET imaging; Phosphorylation; Plasma p-tau217; tau Proteins - blood; Spain; Biomarkers; Healthy controls; Early diagnosis; Plasma p-tau217; Alzheimer’s Disease; Longitudinal
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-024-01642-1

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 ε4 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 ε4 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, ApoE 4 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.