Abstract
Alzheimer's disease (AD) is the most prevalent type of dementia and its pathology is characterized by deposition of extracellular β-amyloid plaques, intracellular neurofibrillary tangles, and extensive neuron loss. While only a few familial AD cases are due to mutations in three causative genes (APP, PSEN1, and PSEN2), the ultimate cause behind the rest of the cases, called sporadic AD, remains unknown. Current animal and cellular models of human AD, which are based on the Aβ and tau hypotheses only, partially resemble the familial AD. As a result, there is a pressing need for the development of new models providing insights into the pathological mechanisms of AD and for the discovery of ways to treat or delay the onset of the disease. Recent preclinical research suggests that stem cells can be used to model AD. Indeed, human induced pluripotent stem cells can be differentiated into disease-relevant cell types that recapitulate the unique genome of a sporadic AD patient or family member. In this review, we will first summarize the current research findings on the genetic and pathological mechanisms of AD. We will then highlight the existing induced pluripotent stem cell models of AD and, lastly, discuss the potential clinical applications in this field.
Highlights
Since Alzheimer’s disease (AD) was first diagnosed by Dr Alois Alzheimer in 1906 [1], it has become the most prevalent neurodegenerative disease overall
To avoid shortcomings brought by viral vector interaction, nonintegrating viruses have been applied for generation of the induced pluripotent stem cell (iPSC), including Adenovirus [56] and Sendai Virus [57,58,59,60]
More alternatives for nonintegrating methods were invented such as transfection miRNA for transcription factors [61], episomal plasmids, three oriP/EBNA plasmids harboring either an Oct4, Sox2, Nanog, and Klf4, an Oct4, Sox2, and SV40 large Tantigen, or a c-myc and Lin28 combination
Summary
Since Alzheimer’s disease (AD) was first diagnosed by Dr Alois Alzheimer in 1906 [1], it has become the most prevalent neurodegenerative disease overall. There is a pressing need for the emergence of new technologies and models reflecting the progression of AD in patients, Stem Cells International confirming the disease pathology, and predicting novel or optimal therapeutic strategies. Since its creation in 2006 by Yamanaka groups, induced pluripotent stem cell (iPSC) is considered as a potential tool for modeling neurodegenerative diseases [9]. By forced expression of certain genes, including Oct 3/4, Sox, Klf, and c-Myc, patients’ specific somatic cells are reprogrammed towards their pluripotent state. In this manner, iPSCs are generated artificially and regain the ability to convert into any cell type of the three germ layers: mesoderm, ectoderm, and endoderm. We summarize the current research on the pathogenesis and iPSC-based models of AD and highlight the potential future application of these cells
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