Angiotensin‐(1‐7)/Mas receptor agonist: a disease modifying therapeutic for VCID protects cognitive function and inhibits serum neurofilament light protein

Vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer’s disease related dementias (ADRD) are associated with increases in systemic and brain inflammatory cytokines, increased reactive oxygen species (ROS) and decreased brain blood flow. We have completed preclinical development of novel synthetic glycopeptide derivatives of Angiotensin‐(1‐7) (Ang‐1‐7) MasR agonists that have outstanding brain penetration, improved half‐life, reverse cognitive impairment and decreases plasma neurofilament light protein (NfL) in our preclinical model of VCID. Ang‐(1‐7)/MasR mechanisms of action include inhibition of 1) microglia activation, 2) brain cytokines activation and, 3) vascular endothelial ROS production. The purpose of this pilot study was to 1) determine if plasma NfL is increased in coronary artery bypass graft (CABG) surgery patients at‐risk for VCID and 2) determine if treatment with an Ang‐(1‐7)/MasR agonist protects cognitive function post‐surgy and modifies NfL.