What they did

  • Alzheimer’s disease is a neurodegenerative disorder characterized by memory loss and cognitive decline.
  • Amyloid-beta (Aβ) plaques and tau neurofibrillary (P-tau) tangles have been found in the brain and are known to disrupt neuron communication causing cell death and over all shrinking of the brain.
  • Current treatments for Alzheimer’s are medications that can help slow the advancement of the disease and manage some symptoms but can’t reverse the effects of the neurodegeneration.
  • Exosomes are small (nanoparticle) vesicles of information that come from neural stem cells (NSCs)  and can promote communication between cells.
  • They are able to cross the blood brain barrier making them a promising option for helping with brain related diseases. 
  • This study looks at the possible protective effects NSC-exos have against AD.

How they did it

  • Human neural stem cells were grown in a nutrient-rich solution. Once these cells covered 90% of the surface, exosomes were collected and placed into a saltwater solution.
  • The exosomes from neural stem cells (NSCs-exos) were then added to a neurodegenerative disease culture model to study their effects.
  • The activity of key enzymes, such as β-secretase, γ-secretase, acetylcholinesterase, GSK-3β, and CDK5, was measured. These enzymes are important in the production of amyloid-beta (Aβ) and phosphorylated tau (p-tau).
  • Levels of amyloid-beta (Aβ) and p-tau in neuroblastoma cells treated with the stem cell exosomes were measured using ELISA.
  • Gene expression related to Alzheimer’s disease (e.g., ADAM10, BACE1, PSEN1, GSK-3β, and CDK5) was analyzed.
  • Western blotting was used to determine the levels of p-tau and other proteins in the treated group.
  • The number of inflammatory markers was measured to evaluate the anti-inflammatory effects of the exosomes.
  • The number of live cells was counted to assess the viability of cells treated with exosomes.

What they found 

  • NSC-exos treatment significantly reduced enzyme activity, suggesting a protective effect against the development of amyloid-beta (Aβ) and phosphorylated tau (p-tau).
  • RT-PCR analysis showed that NSC-exos down-regulated genes linked to the production of Alzheimer’s risk factors.
  • ELISA results found significantly lower levels of Aβ and p-tau in cells treated with NSC-exos compared to control cells.
  • Cells treated with NSC-exos lived longer than control cells, indicating their potential to prevent cell death.
  • NSC-exos reduced inflammation levels and down-regulated pathways that are risk factors for Aβ and p-tau.

What it means

  • The study shows that NSC-exos have potential to effectively reduce neuroinflammation and neurodegeneration by changing key pathways and reducing toxic protein build up.
  • NSC-exos have their effects by enhancing certain genes that help restrict the production of other harmful genes and reduce levels of inflammation related to AD risk factors.
  • Compared to direct stem cell therapies, NSC-exos are less likely to trigger immune responses or tumor growth. They are also easier to produce, store, and administer.
  • Overall, this study is promising for the future of clinical applications for AD.

Clinical uses

  • This study shows that NSC-exos can significantly reduce levels of Aβ and p-tau levels, lower levels of neuroinflammation, and improves cell longevity, highlighting their potential as a clinical application for AD.
  • While more research needs to be done to better understand how MSC-exos can be used in humans and clinical applications, this study is a very promising in showing how these cells work to combat AD factors.

Link to original article

Khan, M.I., Jeong, E.S., Khan, M.Z. et al. Stem cells-derived exosomes alleviate neurodegeneration and Alzheimer’s pathogenesis by ameliorating neuroinflammation, and regulating the associated molecular pathways. Sci Rep 13, 15731 (2023). https://doi.org/10.1038/s41598-023-42485-4

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