Age‐related increase in plasma p‐tau217 in amyloid‐beta–negative cognitively unimpaired individuals affects diagnostic interpretation

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.