Objective:

To determine whether plasma p-tau181 is associated with prevalent and incident cardiovascular disease (CVD). 

Background:

Plasma p-tau181 is a promising AD biomarker for clinical use that has been demonstrated to accurately identify clinical Alzheimer’s disease(AD), align with AD pathology on autopsy, and predict future cognitive decline in research cohorts. However, recent studies in clinical cohorts have raised concerns regarding the effect of medical comorbidities, such as cardiovascular and renal disease, on plasma p-tau181 specificity. These influences must be better understood to enable appropriate clinical use of p-tau181. We sought to evaluate the association between p-tau181 and CVD outcomes in the Framingham Heart Study(FHS). 

Design/Methods:

The FHS is a community-based longitudinal cohort study with deep-phenotyping of CVD. P-tau181 levels were measured from stored samples of 2543 participants from 2011-2014 (Offspring and Omni Cohorts, age 71±8, 55% female, 22% APOE4+) using Quanterix Simoa. CVD outcomes (binary:yes/no) included coronary heart disease, congestive heart failure(CHF), stroke/TIA, and peripheral arterial disease. Multivariate logistic regressions were performed to assess the association between p-tau181 and each prevalent CVD outcome adjusting for age, sex, cohort, eGFR, and BMI. Cox regression models were performed to assess the association between p-tau181 and incident CVD outcomes adjusting for similar covariates after a median follow-up of 7.0 years [5.8-7.6]). 

Results:

At baseline, elevated p-tau181 was associated with prevalent CHF(OR 1.73; 95%CI[1.01-2.97]). Longitudinally, elevated p-tau181 was associated with greater future risk of CHF (HR 1.54[1.02-2.32]). There was no association between p-tau181 levels and other CVD outcomes in cross-sectional or longitudinal analyses. 

Conclusions:

Plasma p-tau181 levels are associated with prevalent and incident CHF in a community-based population. This suggests p-tau181 levels should be interpreted with caution in patients with CHF until the link between p-tau181 and CHF can be further evaluated. Studies to understand medical comorbidities that influence plasma AD biomarkers are necessary prior to widespread clinical use.