Exploring the Cellular and Molecular Mechanisms Underlying Alzheimer's Disease Utilizing Cerebral Organoids Derived from Patient-specific Induced Pluripotent Stem Cells (iPSCs): A Review with Implications for Surgical Interventions

Alzheimer's disease (AD) remains a major unmet medical need characterized by progressive cognitive decline and multifactorial pathology. Induced pluripotent stem cell (iPSC) technology provides an invaluable platform to model patient-specific and late-onset disease mechanisms. Advances in reprogramming strategies and neuronal differentiation protocols have improved the fidelity of human-derived neuronal models by preserving age-related and epigenetic features relevant to AD. Cortical organoids generated from iPSCs have further enabled the reconstruction of three-dimensional brain-like structures, facilitating the study of amyloid and tau pathology, synaptic dysfunction, and neuroinflammatory interactions in a physiologically relevant context. Ongoing innovations, such as microglial integration, vascularization, and induction of cellular aging, continue to enhance the translational accuracy of these models. iPSC and organoid systems are increasingly used for mechanistic dissection of AD-related pathways, genotype-phenotype correlations, and high-throughput therapeutic screening. Nevertheless, challenges related to reproducibility, maturation, and scalability remain barriers to clinical translation. The review also highlights ethical, regulatory, and societal considerations inherent to human stem cell-based disease modeling. Together, these developments underscore the transformative potential of iPSC-derived models in advancing mechanistic understanding and therapeutic discovery for Alzheimer's disease.