Abstract
Background:Neurodegenerative diseases like Alzheimer’s Disease (AD) are a global health issue primarily in the elderly. Although AD has been investigated using primary cultures, animal models and post-mortem human brain tissues, there are currently no effective treatments.Summary:With the advent of induced pluripotent stem cells (iPSCs) reprogrammed from fully differentiated adult cells such as skin fibroblasts, newer opportunities have arisen to study the pathophysiology of many diseases in more depth. It is envisioned that iPSCs could be used as a powerful tool for neurodegenerative disease modelling and eventually be an unlimited source for cell replacement therapy. This paper provides an overview of; the contribution of iPSCs towards modeling and understanding AD pathogenesis, the novel human/mouse chimeric models in elucidating current AD pathogenesis hypotheses, the possible use of iPSCs in drug screening, and perspectives on possible future directions.Key messages:Human/mouse chimeric models using iPSCs to study AD offer much promise in better replicating AD pathology and can be further exploited to elucidate disease pathogenesis with regards to the neuroinflammation hypothesis of AD.
Highlights
Alzheimer’s Disease (AD) is the most common type of neurodegenerative disease, affecting about 30 million people worldwide and almost a million people in the UK [1]
In other PSEN1 mutant models, such as the L166P mutation which is known to cause an aggressive form of familial AD (FAD), the Aβ42/40 ratio was higher after overexpressing PSEN1 but this was due to a large decrease in Aβ40 peptides in the L166P neurons [34]
This review focuses on neuronal pathology and lines where amyloid metabolism is affected, it needs to be acknowledged that other induced pluripotent stem cells (iPSCs) lines have been generated
Summary
Neurodegenerative diseases like Alzheimer’s Disease (AD) are a global health issue primarily in the elderly. AD has been investigated using primary cultures, animal models and post-mortem human brain tissues, there are currently no effective treatments. It is envisioned that iPSCs could be used as a powerful tool for neurodegenerative disease modelling and eventually be an unlimited source for cell replacement therapy. This paper provides an overview of; the contribution of iPSCs towards modeling and understanding AD pathogenesis, the novel human/mouse chimeric models in elucidating current AD pathogenesis hypotheses, the possible use of iPSCs in drug screening, and perspectives on possible future directions.
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