Published online May 26, 2019. doi: 10.4252/wjsc.v11.i5.236
Peer-review started: January 16, 2019
First decision: January 29, 2019
Revised: February 22, 2018
Accepted: March 26, 2019
Article in press: March 26, 2019
Published online: May 26, 2019
Alzheimer’s disease (AD) is the most common form of dementia. To date, only five pharmacological agents have been approved by the Food and Drug Administration for clinical use in AD, all of which target the symptoms of the disease rather than the cause. Increasing our understanding of the underlying pathophysiology of AD will facilitate the development of new therapeutic strategies. Over the years, the major hypotheses of AD etiology have focused on deposition of amyloid beta and mitochondrial dysfunction. In this review we highlight the potential of experimental model systems based on human induced pluripotent stem cells (iPSCs) to provide novel insights into the cellular pathophysiology underlying neurodegeneration in AD. Whilst Down syndrome and familial AD iPSC models faithfully reproduce features of AD such as accumulation of Aβ and tau, oxidative stress and mitochondrial dysfunction, sporadic AD is much more difficult to model in this way due to its complex etiology. Nevertheless, iPSC-based modelling of AD has provided invaluable insights into the underlying pathophysiology of the disease, and has a huge potential for use as a platform for drug discovery.
Core tip: Alzheimer’s disease (AD) is a huge burden on the healthcare system and on society. At present, there are no therapeutic approaches that address the underlying causes of this devastating disease, largely because we lack understanding of the underlying molecular mechanisms. Induced pluripotent stem cells (iPSCs) from AD or Down syndrome patients can be used to elucidate these molecular mechanisms, therefore presenting a novel approach to this problem. In this review, we focus on the ability of iPSC models to gain insight into the mitochondrial dysfunction that occurs during AD and therefore identify novel drug targets.