Neural Stem Cells in the Treatment of Alzheimer’s Disease: Current Status, Challenges, and Future Prospects

Abstract

Alzheimer’s disease (AD), a progressive dementia, is one of the world’s most dangerous and debilitating diseases. Clinical trial results of amyloid-β (Aβ) and tau regulators based on the pretext of straightforward amyloid and tau immunotherapy were disappointing. There are currently no effective strategies for slowing the progression of AD. Further understanding of the mechanisms underlying AD and the development of novel therapeutic options are critical. Neurogenesis is impaired in AD, which contributes to memory deficits. Transplanted neural stem cells (NSCs) can regenerate degraded cholinergic neurons, and new neurons derived from NSCs can form synaptic connections with neighboring neurons. In theory, employing NSCs to replace and restore damaged cholinergic neurons and brain connections may offer new treatment options for AD. However there remain barriers to surmount before NSC-based therapy can be used clinically. The objective of this article is to describe recent advances in the treatment of AD models and clinical trials involving NSCs. In addition, we discuss the challenges and prospects associated with cell transplant therapy for AD.

Potential Stem Cell Treatment for Alzheimer’s Disease with Possible Applications of Lithium Therapy

“…In rodent models affected by alkaline neurotoxicity, the transplantation of human NSCs with high choline acetyltransferase expression has been seen to reverse deficits in spatial memory and learning [68]. In other studies, NSCs are shown to have the potential to protect cerebral capillaries, reduce Aβ and tau pathologies, decrease inflammation, and enhance neurogenesis (Figure 9) [32]. Another study further demonstrated that transplanted human NSCs in the brains of mice effectively reduce Tau phosphorylation levels [74].…”

“…Neural stem cells (NSCs) are another possible candidate for Alzheimer's disease. When NSCs are transplanted, they have the potential to renew deteriorated cholinergic neurons, and new neurons originating from NSCs can establish synaptic links with nearby neurons [32]. The utilization of NSCs to replace and rehabilitate impaired cholinergic neurons and neural connections in the brain presents another theoretical avenue for exploring treatment possibilities for Alzheimer's disease [32].…”

Induced neural stem cells suppressed neuroinflammation by inhibiting the microglial pyroptotic pathway in intracerebral hemorrhage rats

“…NSCs have been considered to possess valuable potential to treat cerebral diseases for which present therapies are almost unavailable due to their ability to differentiate into neurons and glial cells or their paracrine mechanisms. 31 , 32 …”

Potential injectable hydrogels as biomaterials for central nervous system injury: A narrative review

“…NSCs stimulate endogenous synaptogenesis, which improves cognition. However, it is challenging to correctly characterize NSCs' positive effects in AD 41 …”