Arteriosclerosis in the heart-brain axis and Alzheimer's disease plasma markers in the Rotterdam Study

Background Arteriosclerosis in the heart-brain axis has emerged as an important area of study in Alzheimer's disease (AD) dementia research. While previous research primarily focused on structural brain changes, the relationship between arteriosclerosis and blood-based markers for AD dementia remains understudied. Objective To comprehensively assess arteriosclerosis in the heart-brain axis and investigate its link to AD dementia plasma markers. Methods Analyses are based on 2238 community-dwelling elderly from the population-based Rotterdam Study (52% female, mean age 69.5 ± 6.8 years) who underwent a non-contrast CT scan to quantify arteriosclerosis in the heart-brain axis. Coronary artery calcification, aortic arch calcification, extracranial carotid artery calcification, intracranial carotid artery calcification, and vertebrobasilar artery calcification were measured as proxies for arteriosclerosis. Participants had available total tau, neurofilament light chain (NfL), and amyloid-β (Aβ 40 , Aβ 42 , and Aβ 42/40 ratio) plasma measures (median time difference between CT scan and plasma measurement 3.2 months). Using linear regression, we studied the relationship of calcification presence and burden in the abovementioned arteries with plasma markers. Results A higher arteriosclerosis burden correlated with higher plasma marker concentrations, especially for NfL (e.g., β intracranial carotid : 0.15, [95% Confidence interval (CI): 0.04, 0.26]) and Aβ 40 (e.g., β intracranial carotid : 0.18, [95% CI: 0.05, 0.30]). Additionally, vertebrobasilar artery calcification was most consistently associated with elevated levels of AD dementia plasma markers (e.g., total tau; β: 0.06. [95% CI: 0.01, 0.10]). Conclusions Our findings emphasize the critical role of vascular health in neurodegenerative processes and underscore the importance of monitoring and managing arteriosclerosis.