Targeting Shared Mechanisms in Atherosclerosis and Alzheimer's Disease

Atherosclerosis and Alzheimer's Disease are two significant health concerns characterised by overlapping pathophysiological mechanisms, including chronic inflammation, oxidative stress, and lipid metabolism dysregulation. Impaired vascular integrity in atherosclerosis enhances the accumulation of Aβ plaque in the brain by reducing cerebral perfusion and compromising the clearance of Aβ. This review examines the shared pathways linking these conditions, emphasizing the role of the NLRP3 inflammasome, Receptor for Advanced Glycation End Products, and the apolipoprotein E4 allele in exacerbating vascular dysfunction that promotes neurodegeneration. The interplay between these factors underscores the potential of targeting these common pathways as a therapeutic strategy for both diseases. In preclinical studies, emerging treatments, NLRP3 inflammasome inhibitors like MCC950 and CY-09, show promise in mitigating both arterial plaque formation and neuronal amyloid deposition, while innovative microRNA-based therapies targeting miR-146a and miR-155 offer novel approaches to reduce inflammatory responses. Additionally, modulation of lipid metabolism through liver X receptor agonists like T0901317 and cholesteryl ester transfer protein inhibitors, including Anacetrapib, offers potential dual benefits for cardiovascular and neurological health. However, challenges such as restricted BBB permeability, genetic and sex variability, and limited long-term clinical evidence continue to constrain the effectiveness of dual-targeted therapeutic approaches. Future perspectives suggest integrating multi-- modal therapies that combine anti-inflammatory, lipid-regulatory, and antioxidant strategies to effectively address these interrelated diseases. Advancements in molecular biology and imaging techniques may facilitate the development of personalised medicine approaches, ultimately improving outcomes for patients suffering from both atherosclerosis and Alzheimer's Disease.