From Bench to Bedside: Cutting-Edge and Emerging Therapies for Alzheimer's Disease

Alzheimer's disease (AD) remains one of the most pressing neurodegenerative disorders worldwide, with increasing prevalence and limited disease-modifying treatments. While recent clinical advances, including monoclonal antibodies like lecanemab and donanemab (early stage), show promise in slowing cognitive decline by targeting amyloid-beta pathology, their use is associated with risks such as amyloid-related imaging abnormalities (ARIA). Alongside these developments, preclinical innovations continue to explore novel mechanisms, including antisense oligonucleotides, TREM2 agonists, siRNA, mRNA-LNP platforms, and CRISPR-based gene editing. These approaches target tau aggregation, neuroinflammation, and genetic risk modifiers like APOE4. This review bridges the gap between preclinical research and clinical application by highlighting the mechanisms, therapeutic potential, and translational challenges of both established and emerging therapies. Emphasis is placed on biomarker-guided trials, model systems (e.g., iPSC organoids), and future directions to improve efficacy, safety, and global accessibility of AD therapeutics.