Understanding Alzheimer’s Disease Through Neurodevelopment: Insights from Human Cerebral Organoids

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, for which there is currently no cure. The causes of AD are still not well understood, although 5% of cases are known to have a genetic origin, associated with pathogenic genetic variants of the APP and PSEN1/2 genes. There is growing evidence that both APP and PSEN1/2 are also essential for proper human brain development and neural/neuronal function. This implies that abnormalities in early brain development could increase neuronal vulnerability to AD later in life. Human cerebral organoids (hCOs), generated from induced pluripotent stem cells (iPSCs) from AD patients, provide an exceptional model for better understanding the cellular and molecular mechanisms involved in human brain development, as well as early neurological alterations in the evolution of AD. This review compiles the main studies in which hCOs are used as a model for studying AD and for the discovery of new biomarkers. We also discuss the advantages and applications of these hCOs for studying the early stages of AD from a neurodevelopmental perspective. Finally, we mention the main current challenges in the use of hCOs for future research into AD.