Advances in Alzheimer’s Disease Research: Human Cerebral Organoids

Abstract

Alzheimer’s disease (AD) is the main neurodegenerative disorder in old age, causing memory impairment and dependency. The histopathology of AD is characterized by the presence of amyloid plaques and neurofibrillary tangles formed by Aβ peptide and hyperphosphorylated Tau, respectively. There is still no cure or effective treatment for AD. This could be due, in part, to the lack of suitable research models since animal models do not recapitulate the full physiological complexity of the human brain. With the development of induced pluripotent stem cells (iPSCs), these limitations could be overcome. Even so, the bi-dimensional (2D) culture models still do not allow to recapitulate all types of brain cells and do not show a three-dimensional (3D) arrangement. Since obtaining 3D cultures called organoids, a new opportunity arises to overcome the limitations of previous models. Human Cerebral Organoids (hCOs) represent a pioneering model, in which part of the complexity of the human brain is present. For this reason, they are fast becoming a very remarkable model for the study of the evolution of the molecular and cellular pathology of AD. This review provides a brief overview of AD research, focusing on the most recent advances achieved through the development of stem cell and cerebral organoid technology