Modeling Sporadic Alzheimer’s Disease by Efficient Direct Reprogramming of the Elderly Derived Disease Dermal Fibroblasts into Neural Stem Cells

2020 ◽  
Vol 73 (3) ◽  
pp. 919-933 ◽  
Author(s):  
Yanying Liu ◽  
Hongmin Wang
2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Alen Zollo ◽  
Zoe Allen ◽  
Helle F. Rasmussen ◽  
Filomena Iannuzzi ◽  
Yichen Shi ◽  
...  

Alzheimer’s disease (AD) is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4) allele. Changes in amyloid precursor protein (APP) binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (Aβ) peptides, which form lethal deposits in the brain. In vivo and in vitro studies have implicated sortilin-related receptor (SORL1) as an important factor in APP trafficking and processing. Recent in vitro evidence has associated the APOE4 allele and alterations in the SORL1 pathway with AD development and progression. Here, we analyzed SORL1 expression in neural stem cells (NSCs) from AD patients carrying null, one, or two copies of the APOE4 allele. We show reduced SORL1 expression only in NSCs of a patient carrying two copies of APOE4 allele with increased Aβ/SORL1 localization along the degenerated neurites. Interestingly, SORL1 binding to APP was largely compromised; this could be almost completely reversed by γ-secretase (but not β-secretase) inhibitor treatment. These findings may yield new insights into the complex interplay of SORL1 and AD pathology and point to NSCs as a valuable tool to address unsolved AD-related questions in vitro.


2017 ◽  
Vol 11 (1) ◽  
pp. 27-38 ◽  
Author(s):  
Godwin Tong ◽  
Pablo Izquierdo ◽  
Rana Arham Raashid

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.


2016 ◽  
Vol 5 (3) ◽  
pp. 379-391 ◽  
Author(s):  
Lisa M. McGinley ◽  
Erika Sims ◽  
J. Simon Lunn ◽  
Osama N. Kashlan ◽  
Kevin S. Chen ◽  
...  

2012 ◽  
Vol 61 (6) ◽  
pp. 885-891 ◽  
Author(s):  
Keun-A Chang ◽  
Jeong a Kim ◽  
Saeromi Kim ◽  
Yuyoung Joo ◽  
Ki Young Shin ◽  
...  

2016 ◽  
Vol 54 (7) ◽  
pp. 5120-5130 ◽  
Author(s):  
Lan Zhao ◽  
Chunlei Zhou ◽  
Li Li ◽  
Jianwei Liu ◽  
Huiyan Shi ◽  
...  

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