Enhanced Neuroprotective Synergy of Atorvastatin and Magnesium L-Threonate in a Rat Model of Alzheimer's Disease Induced by Aluminum Chloride

Introduction: Alzheimer's disease (AD) is a widespread neurodegenerative condition with complex causes and a significant global impact, particularly among the elderly. This brief introduction emphasizes AD's hallmark features and the urgent public health concern it poses, with numbers on the rise. It also highlights the potential of statins and magnesium L-threonate as a combined therapeutic approach to prevent AD and mitigate its underlying pathological features. The study's goal is to shed light on these promising interventions in a rat model induced by aluminum chloride (AlCl3). Materials and methods: A total of 30 aged female Wistar rats were divided into five groups (n=6/group). The vehicle control group received normal saline orally (p.o.). The model control group received AlCl3 (4.2 mg/kg/day intraperitoneal (i.p.)). The standard-treated group received rivastigmine (1 mg/kg/day p.o.), and the atorvastatin-treated and atorvastatin with magnesium L-threonate-treated groups received atorvastatin (20 mg/kg/day p.o.) and atorvastatin (20 mg/kg/day) with magnesium L-threonate (604 mg/kg/day p.o.), respectively. Cognitive functions such as radial arm maze, elevated plus maze (EPM), passive shock avoidance test, and open-field test (OFT) were performed at weekly intervals up to 28 days. After completion of the study on the 29th day, all animals were sacrificed, and the brain was used for estimation of AchE enzyme activity, oxidative stress parameters, and histopathological analysis. Result: At the end of the fourth week, administration of atorvastatin and atorvastatin with magnesium L-threonate resulted in a decreased average time taken to reach the correct arm, reduced transfer latency (TL) in the EPM, shortened latency to reach the shock-free zone (SFZ), and an increase in rearing and counts by locomotion activity in the OFT. It also demonstrated improved anti-cholinesterase activity and suppressed oxidative stress, as indicated by a decrease in nitric oxide (NO) levels and an increase in superoxide dismutase (SOD) and catalase levels. Additionally, it led to reductions in brain changes observed in histopathological analysis. Conclusion: Atorvastatin with magnesium L-threonate provides a better beneficial protective effect against AD than atorvastatin alone. This combination can be a first choice for patients who are already taking atorvastatin in the early stages of AD.