Alamandine Rescues Cognitive Impairment and Ameliorates Alzheimer’s Disease-Like Neuropathology in APP/PS1 Mice

Alzheimer’s disease (AD) is on the rise worldwide, consequently driving a growing demand for effective prevention and treatment strategies. Alamandine is a member of the renin–angiotensin system family. Although alamandine exhibits protective effects in the pathophysiology of various disorders, its role in AD remains an unexplored area. This research aims to elucidate the benefits and mechanisms of alamandine in an in vivo model of AD. The mice received intracerebroventricular injections of vehicle or alamandine once daily for 4 weeks. The Morris water maze was conducted to assess spatial learning ability. Nissl staining was performed to evaluate neuronal injury. Important inflammation indictors were detected both by qRT-PCR and ELISA. Representative oxidative stress indicators and Fe²⁺ levels were measured using corresponding assay kits. Western blot was employed to detect the expression levels of the related proteins. We found that alamandine mitigates cognitive function and spatial learning impairment in APP/PS1 mice. Alamandine shows positive therapeutic effects by ameliorating the phosphorylation of tau proteins and suppressing neuroinflammation. In addition, alamandine mitigates the oxidative stress, ferroptosis and endoplasmic reticulum stress (ERS) in the brain of APP/PS1 mice. Our research indicates that alamandine alleviates cognitive impairment in APP/PS1 mice and inhibits inflammation, oxidative stress, ferroptosis, and ERS. It may serve as a promising approach to alleviate symptoms and promote remission in AD.