INDUCING NEUROGENESIS IN PATIENTS WITH

ALZHEIMER’S DISEASE BY STEM CELL THERAPY

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder which impairs the memory and
intellectual abilities of the affected individuals. Loss of episodic as well as semantic memory is an early
and principal feature.
AD manifests as an impaired ability to comprehend or use words, poor coordination and gait, and
impaired executive functions in the realms of planning, ordering and making judgments. Most often,
Alzheimer disease is diagnosed in elderly people, though it can attack younger population, as well.
The basal forebrain cholinergic system is the population of neurons most affected by the
neurodegenerative process. Neuropathological hallmarks of AD are,
• Extracellular as well as intracellular deposition of beta-amyloid or Abeta (Abeta) protein
• Intracellular formation of neurofibrillary tangles and,
• Neuronal loss

Generally followed Treatment protocol for AD

• Deposits of Aβ are a pathological hallmark of AD, and thus depleting Aβ should be a useful
therapy for AD. Cathepsin B is a cysteine protease of the papain superfamily, and degrades
peptides and proteins that enter the endolysosomal system by endocytosis or phagocytosis.
• Glutathione is an antioxidant in brain cells. It reacts with ROS and oxidized products forming
gluthathione disulphide.
• Vitamin E is another endogenous antioxidant that protects against lipid peroxidation, and high
levels of vitamin E have been shown to be related to a reduced risk of AD. Vitamin C is a watersoluble
antioxidant that is necessary for the reactivation of vitamin E. Although vitamins C and
E have been used in clinical applications to prevent AD, no clear beneficial effect has been
demonstrated.

For the most part, pharmacological interventions are aimed at relieving the symptoms of AD, but stem
cell therapy not only has the potential to generate new neurons and replace damaged neurons but also
to modulate the immune system

Mechanism of Action Stem Cell Therapy which aids in AD treatment:

Stem cells include embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and tissuederived
stem cells, such as bone marrow (BM) and adipose-derived stem cells.
1. Stem cells exhibit targeted migration towards the damaged regions of the brain, where they
engraft, proliferate and mature into functional neurons. Neural precursor cells can be
intravenously administered and yet migrate into brain damaged areas and induce functional
recovery.
2. Transplanted stem cells or neural precursor cells (NPCs) survive, migrate, and differentiate into
cholinergic neurons, astrocytes, and oligodendrocytes with amelioration of the learning/memory
deficits.
3. Bone marrow derived mesenchymal stem cells (BMMSCs) are able to home in on the injured
brain and increase the number of positive cells for choline acetyltransferase. Furthermore,
BMMSCs not only remove Aβ plaques from the hippocampus but also reduce Aβ deposits
through the activation of endogenous microglia.
4. Besides replacement of lost or damaged cells, stem cells stimulate endogenous neural
precursors, enhance structural neuroplasticity, and down regulate proinflammatory cytokines
and neuronal apoptotic death.
5. Stem cells could also be genetically modified to express growth factors into the brain.

What does the future hold for Alzheimer patients?

In the last years, evidence has indicated that the adult brain of mammals preserves the capacity to
generate new neurons from neural stem/progenitor cells. Inefficient adult neurogenesis may contribute
to the pathogenesis of AD and other neurodegenerative disorders. An attempt at mobilizing this
endogenous pool of resident stem-like cells provides another attractive approach for the treatment of
AD.
With further clarification of the mechanisms by which AD progresses, stem cell therapies may well
prove to be both safe and effective treatments. In time, more advanced stem cell therapies hold the
potential for the clinical treatment of this debilitating disease.

FURTHER READINGS:

1. http://www.news-medical.net/news/20151031/Stem-cell-transplantation-may-offer-viable-treatment-for-
Alzheimers-disease-patients.aspx
2. http://www.foxnews.com/health/2016/04/14/researchers-testing-stem-cells-to-treat-alzheimers-in-first-its-kindtrial.
html
3. http://www.medicalnewstoday.com/articles/275582.php
4. https://hsci.harvard.edu/alzheimers-disease-0

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