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
