Author Identifier (ORCID)
Abstract
Introduction: The extent to which non-pathological aging influences plasma biomarkers remains unclear. Here, we investigate factors influencing plasma p-tau217 levels in cognitively unimpaired (CU), amyloid-beta–negative (Aβ-) individuals. Methods: Plasma p-tau217 was measured in CU Aβ- positron emission tomography–negative (PET-) participants using two immunoassays (ALZpath n = 360 and LUMIPULSE G1200 n = 73). Associations between p-tau217 and age groups (60–69, 70–79, and 80+ years), apolipoprotein E (APOE) genotype, and gender were evaluated. Results: ALZpath plasma p-tau217 showed a non-pathological age-related increase (p < 0.001), and increased percentage within the intermediate zone with age. Lumipulse p-tau217 showed an increase in the percentage of subjects with positive results with age, however, this trend was not significant (p > 0.05). Men had higher levels of p-tau217 only with the ALZpath assay (p = 0.02; Lumipulse: p = 0.81). No significant associations were found between p-tau217 and APOE genotype. Discussion: Our results highlight the importance of incorporating age and sex into the interpretation of plasma p-tau217 particularly in preclinical stages.
Keywords
Alzheimer's disease, biomarkers, cognitively normal, normal aging, plasma p-tau217
Document Type
Journal Article
Date of Publication
6-1-2026
Article Number
e71532
ISSN
15525260
Volume
22
Issue
6
PubMed ID
42251493
Publication Title
Alzheimer's & Dementia
Publisher
Wiley
School
School of Medical and Health Sciences
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Recommended Citation
Mammel, A. E., Gonzalez‐Ortiz, F., Mousavi, A., Hallett, K., Encarnacion, M., Biehl, D., Gill, P., Ismael, S., Fowler, C., Doecke, J. D., Ward, L., & Frykman, H. (2026). Age‐related increase in plasma p‐tau217 in amyloid‐beta–negative cognitively unimpaired individuals affects diagnostic interpretation. Alzheimer’s & Dementia, 22(6), e71532. https://doi.org/10.1002/alz.71532