INTRODUCTION

Plasma phosphorylated tau (p-tau) levels, such as p-tau181, are elevated in Alzheimer's disease compared to cognitively unimpaired individuals. They represent potential candidate blood biomarkers for use in memory services where CSF examinations are not available. However, the effect of age on plasma p-tau levels remains undetermined. Limited studies have investigated the association between age and plasma p-tau thus far, and fewer still have differentiated levels by brain amyloid pathology. Characterising these associations and determining if this is influenced by sociodemographic factors or medical comorbidities is important for establishing blood biomarker reference ranges.

METHODS

Using ADNI data, we analysed 860 observations (581 participants; age range: 55-95 years; 56.0% male; 93.6% White). Linear mixed models (LMMs) estimated fixed effects of age, creatinine, baseline BMI, sex, ethnicity, and group (Control vs. AD) on plasma p-tau181 concentration, with a random intercept for participant ID. Separate LMMs assessed covariate effects and interactions with group status.

RESULTS

Analysis of ADNI data revealed a significant positive association between p-tau181 levels, group status, and creatinine in the fully adjusted LLM. Group status may have obscured the total effect of age on p-tau181, as its removal from the model resulted in a significant age effect. Single-variable models showed the positive association between either age, or creatinine and p-tau181 levels did not differ between control and AD groups. There was a significant negative association between BMI and plasma p-tau, which was stronger in AD versus control groups.

CONCLUSIONS

This study provides insights into the factors that may influence plasma p-tau181 levels. These findings underscore the need to account for clinical and demographic factors when interpreting p-tau181. Future research should validate these associations in diverse populations and explore underlying mechanisms.