Brain Organoids as Precision Models for Neurodegenerative Diseases: From Disease Modeling to Drug Discovery

Yanxu Zheng^1,2Wenke Zhou²Haozhe Chang²Kuihong Zheng^1*

• ¹Sixth Medical Center of PLA General Hospital, Beijing, China
• ²Central South University Xiangya School of Medicine, Changsha, China

Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) have become major global causes of disability and mortality. Their complex pathogenic mechanisms remain incompletely understood, and effective disease-modifying therapies are still lacking. Traditional animal models and two-dimensional (2D) cell culture systems exhibit notable limitations in structural complexity, human relevance, and translational validity, making it difficult to faithfully recapitulate human-specific neuropathology. In recent years, brain organoid technology derived from induced pluripotent stem cells (iPSCs) has advanced rapidly, enabling the self-organization of diverse neuronal and glial cell types within a three-dimensional (3D) architecture that partially mimics human brain development and disease-related pathological events. When integrated with CRISPR–Cas9-based genome editing and multi-omics profiling, organoids support causal mechanism studies, target validation, and individualized drug-response prediction, highlighting their growing value in early-stage drug discovery. Despite current challenges—including insufficient maturation, lack of vascularization and immune components, and batch variability—the continuous progress in bioengineering, microfluidic systems, and artificial intelligence (AI)–driven multimodal data analysis is steadily expanding the translational potential of organoids as human-relevant preclinical models. Overall, brain organoids provide an essential foundation for constructing physiologically relevant and predictive research platforms for neurodegenerative diseases, offering new opportunities for therapeutic development and precision medicine.