Deciphering Alzheimer's disease: Molecular mechanisms, preclinical models and strategies to overcome Blood-Brain-Barrier.

Neurodegenerative diseases involve a spectrum of diseases, with Alzheimer's being the most prevalent one. Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline, memory loss, and synaptic dysfunction. Despite extensive research, effective therapeutic interventions remain limited, largely due to the complex molecular underpinnings of the disease and the challenge posed by the blood-brain barrier (BBB). This review explores the critical molecular mechanisms implicated in AD pathogenesis, i.e. disruption of cholinergic neurotransmission, aggregation of β-amyloid fragments, tau protein phosphorylation, and oxidative stress. As the establishment of effective treatments remains a major research goal, the present review further gives an insight into the various preclinical in vivo models like chemical, lesion-induced, beta-amyloid, streptozotocin infusion, and transgenic models that have been instrumental in advancing our understanding of disease progression and testing potential treatments. A significant focus is given to emerging strategies designed to circumvent or modulate the BBB, including nanoparticle-based delivery systems, receptor-mediated transport, and focused ultrasound techniques. By integrating insights from molecular biology, experimental modeling, and drug delivery science, this work aims to highlight current challenges and propose comprehensive strategies for improving the diagnosis and treatment of Alzheimer's disease.