Vascular Risk and β-Amyloid Are Synergistically Associated with Cortical Tau

Objective Neuropathological studies have demonstrated that cerebrovascular disease and Alzheimer disease (AD) pathology frequently co-occur in older adults. The extent to which cerebrovascular disease influences the progression of AD pathology remains unclear. Leveraging newly available positron emission tomography (PET) imaging, we examined whether a well-validated measure of systemic vascular risk and beta-amyloid (A beta) burden have an interactive association with regional tau burden. Methods Vascular risk was quantified at baseline in 152 clinically normal older adults (mean age = 73.5 +/- 6.1 years) with the office-based Framingham Heart Study cardiovascular disease risk algorithm (FHS-CVD). We acquired A beta (C-11-Pittsburgh compound B) and tau (F-18-flortaucipir) PET imaging on the same participants. A beta PET was performed at baseline; tau PET was acquired on average 2.98 +/- 1.1 years later. Tau was measured in the entorhinal cortex (EC), an early site of tau deposition, and in the inferior temporal cortex (ITC), an early site of neocortical tau accumulation associated with AD. Linear regression models examined FHS-CVD and A beta as interactive predictors of tau deposition, adjusting for age, sex, APOE epsilon 4 status, and the time interval between baseline and the tau PET scan. Results We observed a significant interaction between FHS-CVD and A beta burden on subsequently measured ITC tau (p < 0.001), whereby combined higher FHS-CVD and elevated A beta burden was associated with increased tau. The interaction was not significant for EC tau (p = 0.16). Interpretation Elevated vascular risk may influence tau burden when coupled with high A beta burden. These results suggest a potential link between vascular risk and tau pathology in preclinical AD. Ann Neurol 2019; 1-8 ANN NEUROL 2019;85:272-279.