MODELING ALZHEIMER'S DISEASE WITH INDUCED PLURIPOTENT STEM CELLS (IPSCS): PROGRESS, CHALLENGES, AND TRANSLATIONAL OPPORTUNITIES

Alzheimer's Disease (AD) is the most prevalent neurodegenerative disorder globally, affecting approximately 55 million individuals in 2019, predicted to impact 139 million by 2050. Although it remains a devastating force in public health, it has proved difficult to achieve effective disease-modifying treatments. This review examines the emerging role of human-induced pluripotent stem cells (hiPSCs) in AD research and therapeutic development. Demonstrating an incredible capacity to recapitulate AD pathological features such as abnormal amyloid-β accumulation, elevated Aβ42/Aβ40 ratios, tau hyperphosphorylation, and network hyperexcitability, neurons derived from hiPSCs have presented themselves as a promising platform for studying the mechanisms of AD and facilitating drug screening. Their efficacy is reinforced by innovations such as 3D bioengineered scaffolds. Engineered tissues spontaneously developed the characteristics of AD that typically only emerge with prolonged maturation. While some limitations and weaknesses still need to be overcome, this review explores advancements such as organoid systems, co-cultures, and CRISPR-engineered isogenic controls that directly address these challenges.