scholarly journals 3D Culture Method for Alzheimer's Disease Modeling Reveals Interleukin-4 Rescues Aβ42-Induced Loss of Human Neural Stem Cell Plasticity

2018 ◽  
Vol 46 (1) ◽  
pp. 85-101.e8 ◽  
Author(s):  
Christos Papadimitriou ◽  
Hilal Celikkaya ◽  
Mehmet I. Cosacak ◽  
Violeta Mashkaryan ◽  
Laura Bray ◽  
...  
2012 ◽  
Vol 8 (4S_Part_16) ◽  
pp. P577-P578
Author(s):  
Mathew Blurton-Jones ◽  
Rahasson Ager ◽  
Joy Nerhus ◽  
Andy Agazaryan ◽  
Stephen Huhn ◽  
...  

2020 ◽  
Author(s):  
Lauren A Apodaca ◽  
Al Anoud D Baddour ◽  
Camilo Garcia ◽  
Leila Alikhani ◽  
Erich Giedzinski ◽  
...  

Abstract Background: Regenerative therapies to mitigate Alzheimer’s disease (AD) neuropathology have shown very limited success. In the recent era, extracellular vesicles (EV) derived from multipotent and pluripotent stem cells have shown considerable promise for the treatment of dementia and many neurodegenerative conditions. Methods: Using the 5xFAD accelerated transgenic mouse model of AD, we now show the regenerative potential of human neural stem cell (hNSC)-derived EV on the neurocognitive and neuropathologic outcomes in the AD brain. Two or six-month-old 5xFAD mice received single or two intra-venous (retro-orbital vein, RO) injections of hNSC-derived EV, respectively.Results: RO treatment using hNSC-derived EV restored fear extinction memory consolidation and reduced anxiety-related behaviors 4-6 weeks post-injection. EV treatment also significantly reduced dense core amyloid-beta plaque accumulation and microglial activation in both age groups. These results correlated with partial restoration of homeostatic levels of circulating pro-inflammatory cytokines in the AD mice. Importantly, EV treatment protected against synaptic loss in the AD brain that paralleled improved cognition. MiRNA analysis of the EV cargo revealed promising candidates targeting neuroinflammation and synaptic function. Conclusions: Collectively, these data demonstrate the neuroprotective effects of systemic administration of stem cell-derived EV for remediation of behavioral and molecular AD neuropathologies.


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