Promising Prospects for Human Cerebral Organoids to Advance Alzheimer's Disease Research

Abstract

The causes of the alterations found in the brains of patients with alzheimer's disease (AD) begin before the first signs of memory loss appear, and are still unclear. Adequate research models are essential to understand the mechanisms that cause the onset of these alterations, as well as to advance in the diagnosis, development and testing of treatments for the AD. Animal research models fail to recreate the great diversity and complexity inherent to the human brain, so in vitro systems based on human pluripotent stem cells (hPSCs) present themselves as an important alternative. Differentiation of hPSCs into two-dimensional (2D) cell culture models allows recreation of various brain functional processes and the three-dimensional (3D) cell culture models or human brain organoids (hCOs) recapitulate the cellular diversity and structure of the human brain. hCOs from human induced pluripotent stem cells (hiPSCs) from patients with familial (APP, PSEN1 and PSEN2 mutations) or sporadic AD allow identifying and studying changes due to this pathology. This review presents an overview of the research models used to study the AD, and recapitulates the advantages and discusses the challenges of the hCOs as an innovative and promising technology that will aid in the understanding of AD.