The renin-angiotensin system in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of β-amyloid
deposits and hyperphosphorylation of the Tau protein. In recent years, however, a growing body of evidence
has demonstrated that age-related vascular alterations and cardiovascular risk factors play a significant role
in the pathogenesis of AD. Within this context, pharmacological agents targeting the renin-angiotensin
system (RAS), widely prescribed for the treatment of hypertension, have shown considerable potential in
delaying the progression of AD due to their actions on the cerebral RAS. In AD, the pressor axis comprising
ACE/Ang II/AT1R within the RAS is overactivated, contributing to oxidative stress, neuroinflammation,
increased permeability of the blood-brain barrier, astrocyte dysfunction, and reductions in cerebral blood
flow, all of which are hallmark features of the disease. Consistent with these findings, retrospective studies
have reported a decreased risk of developing AD among individuals treated with RAS inhibitors. This
article focuses on the interplay between the RAS and AD.