Patient-derived iPSCs, a reliable in vitro model for the investigation of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease and a common cause of dementia among elderly individuals. The disease is characterized by progressive cognitive decline, accumulation of senile amyloid plaques and neurofibrillary tangles, oxidative stress, and inflammation. Human-derived cell models of AD are scarce, and over the years, non-human-derived models have been developed to recapitulate clinical AD, investigate the disease's pathogenesis and develop therapies for the disease. Several pharmacological compounds have been developed for AD based on findings from non-human-derived cell models; however, these pharmacological compounds have failed at different phases of clinical trials. This necessitates the application of human-derived cell models, such as induced pluripotent stem cells (iPSCs) in their optimized form in AD mechanistic studies and preclinical drug testing. This review provides an overview of AD and iPSCs. The AD-relevant phenotypes of iPSC-derived AD brain cells and the usefulness of iPSCs in AD are highlighted. Finally, the various recommendations that have been made to enhance iPSC/AD modelling are discussed.

Keywords: Alzheimer’s; amyloid-beta; iPSC; integrating; non-integrating; oxidative stress; reprogramming; tau.