Stem Cell For Alzheimer’s Disease: New Alzheimer’s Treatments & Scientific Progress

Introduction

Alzheimer’s is a neurodegenerative disease that destroys an individual’s ability to think and perform daily life tasks. 

Globally, more than 57 million individuals are affected with dementia, among whom Alzheimer’s is the most common. To date, there is no definite cure for Alzheimer’s. The focus remains on supporting individuals and managing the disease symptoms. 

As an emerging therapeutic area, Stem Cell Therapy for Alzheimer’s Treatment focuses on introducing regenerative approaches. The focus remains on reversing the damaged neural cells and replacing them with new cells.

Understanding Alzheimer’s Disease

Alzheimer’s is a progressive neurodegenerative disease, it is characterized by neuronal loss, disruption of the neuronal network, synaptic dysfunction, and decline in cognitive function. The disease pathophysiology is multifactorial. It is the cumulation of molecular, cellular and inflammatory processes. Pathological features involve:

• Accumulation of amyloid-β peptide results in plaque formation, disruption of synaptic signalling, and triggers a neurotoxic cascade.
• Hyperphosphorylation of tau protein forms intracellular neurofibrillary tangles, neuronal death, and impaired axonal transport.

The early symptoms involve forgetting recent events, confusion, disrupting daily life activities, etc. Over time, the severity of symptoms progresses, characterized by memory loss. 

Alzheimer’s Disease Progression Results In

• Formation of Amyloid-β plaques and tau pathology
• Neuroinflammation and synaptic dysfunction
• Progressive neuronal Loss and cognitive decline

Risk Factors

The significant risk factors include:

• Ageing (the most substantial risk factor)
• Genetic Factors (an individual with a family history of Alzheimer’s)
• Environmental & Lifestyle Factors (Metabolic disorder, Heart disease, Hypertension, Obesity)

Symptoms 

Common symptoms of Alzheimer’s include:

• Memory Loss: Disruption of daily life functions (work or personal life)
• Trouble with concentration, thinking and reasoning: Problem with abstract thinking, managing finances
• Judgement & Decision Making: Inability to make sensible decisions or judgments
• Planning or Undertaking Familiar Tasks: Confusion or inability to perform routine activities
• Change in Behaviour or Personality: Depressive mood, Loss of interest in social gatherings, activities, communication, Anger issues, Insomnia, Eating problems, Delusions

How Is Alzheimer’s Treated?

Alzheimer’s is a complex disease. The treatment modality of Alzheimer’s involves opting for one or more options. Some standard Alzheimer’s treatment options include:

• Medications: Cholinesterase inhibitors (Donepezil), N- N-methyl D-Aspartate (NMDA) receptor antagonists (memantine), serotonin reuptake inhibitors (SSRIs) (sertraline, fluoxetine). Administration of amyloid-targeting monoclonal antibodies (donanemab, lecanemab)
• Physical Therapy: Focus on maintaining balance, mobility, and muscle strengthening. Some everyday recommended activities including walking, balance training, and water aerobics
• Behavioural Intervention: Cognitive Behavioural Therapy (CBT), Music and Art Therapy, etc. The focus is to engage individuals in meaningful activities, socialization and creating less confusion. 
• Symptom Management: Recommendation of antidepressants, anti-anxiety, or antipsychotic medication. 
• Environmental Intervention: Maintaining a calm environment, reducing household cluttering, not changing the household objects frequently, dimming lights while sleeping, etc.
• Dietary Intervention: Fresh fruits and vegetables, low-fat diets (low saturated or trans fats), use healthy oils, Mediterranean diet

*NOTE: Conventional Alzheimer’s treatment options are not curative. It focuses on the management of symptoms. 

Stem Cell Therapy for Alzheimer’s Disease

Stem Cell for Alzheimer’s Treatment works with the concept of regenerative medicine in neurodegeneration. The standard type of stem cells studied for Alzheimer’s includes:

• Neural Stem Cells (NSCs)
• Mesenchymal Stem Cells (MSCs)- bone-marrow or umbilical cord-derived
• Embryonic Stem Cells (ESCs)  [1]

Umbilical cord-derived MSCs are mainly studied for stem cell therapy. It possesses the fewest ethical complications and is easy in isolation.

Stem cells undertake two central mechanisms in Alzheimer’s treatments, including:

• Paracrine Neuroprotection- a widely exploited mechanism, stem cells release neuroprotective factors that target proteinopathy.  
• Cell Replacement- stem cells possess regenerative potential; they can replace the damaged cells and promote new cell formation [1]

Biological Mechanisms 

Stem cell for Alzheimer’s disease undertakes crucial biological mechanisms, including:

• Neuroprotection: secretion of neurotrophic factors (BDNF, NGF, EGFR). Supports the survival of neuronal cells, promotes new synapses and neurogenesis
• Reduces Neuroinflammation: reduces the level of pro-inflammatory cytokines (TNF-α, Interleukin-1β), increases the secretion of anti-inflammatory markers (IL-10)
• Support of Synaptic Plasticity and Neuronal Survival: synaptic remodelling by neuronal replacement, promotion of synaptic connections, and improvement of endogenous neurogenesis
• Modulation of Microglial Activation: Secretion of immunomodulatory factor (IL-10, TGF-β), enhanced clearance of amyloid beta plaque [1,2]
• Paracrine Signaling: promotes cell-to-cell communication through the release of anti-inflammatory, neurotrophic growth factors

Preclinical and Clinical Research Evidence

Research evidence in Stem cells for Alzheimer’s disease supports the positive side. The outcomes include:

Key Findings from Animal Models:

• Reduction of amyloid-β burden 
• Enhanced clearance of amyloid plaques 
• Modulation of microglial activity 
• Attenuate neuroinflammation  
• Shift microglia from a pro-inflammatory to a neuroprotective phenotype.
• preservation of hippocampal neurons 

Early-Phase Human Clinical Trials

Preliminary Efficacy

• Reduction in neuroinflammatory marker
• Stabilization incognito decline
• improvements in specific neuropsychological test scores
• Greater paracrine and immunomodulatory mechanisms

Common Administration Route

• Intracerebral 
• Intrathecal
• Intravenous 

Safety Observation

• Stem cell administration displayed a favorable safety profile
• No major serious events were reported in short or mid-term follow-ups

Limitations

• Reversal of neurodegeneration isn’t conclusively
• Long-term safety has not been determined in a larger population

New Alzheimer’s Treatments 2025: Where Do Stem Cells Fit In 

The current research focus remains on the incorporation of stem cell therapy with other treatment options. Some of the widely investigated approaches include:

• Stem cell therapy in combination with drug-based treatments
• Combination approaches (stem cells + biologics/exosomes)
• Promote paracrine signaling through the use of advanced delivery methods or finding cell-free alternatives.

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Challenges, Limitations, and Ethical Considerations

The use of stem cells for Alzheimer’s disease translation from research to clinical application poses particular challenges. Some of the challenges include:

• Cell delivery through–blood-brain barrier (BBB)
• Standardization of the stem cell therapy and scalability
• Ethical and regulatory considerations
• Maintaining similar efficacy in the use of each stem cell batch

Who Can Benefit from Stem Cell Therapy

• An individual experiencing the early to moderate stage of Alzheimer’s
• Patient introduced to personalized medicine 
• Treatment with Long-term regenerative neurology vision
• Advanced study might ensure the curative potential of stem cell therapy for Alzheimer’s

Stem Cell Therapy- Future of Alzheimer’s Treatment 

Stem Cell Therapy for Alzheimer’s Disease offers a compelling scientific promise. It potentially targets the underlying mechanism of disease progression- neuroinflammation, neuronal Loss, and synaptic dysfunction. Preclinical and Clinical study suggests that stem cell administration plays a role in neuroprotection and slow disease progression mediated by paracrine and immunomodulatory effects. 

However, significant limitations remain in the standardization of stem cell therapy administration, challenges in the delivery of cells in the brain and long-term data efficacy. 

Alzheimers Patient Success Stories

Major Takeaways

• Stem cell therapy for Alzheimer’s can potentially slow disease progression 
• Current evidence lacks supportive evidence for the complete reversal of neurodegeneration 
• Stem cell therapy can alter disease trajectory
• Future development requires undertaking rigorous clinical trials 
• Long-term follow-up studies are essential

References

1. Duan Y, Lyu L, Zhan S. Stem cell therapy for Alzheimer’s disease: a scoping review for 2017–2022. Biomedicines. 2023 Jan 3;11(1):120.
2. Qin C, Wang K, Zhang L, Bai L. Stem cell therapy for Alzheimer’s disease: An overview of experimental models and reality. Animal models and experimental medicine. 2022 Feb;5(1):15-26.

FAQ’s

Q- What is Alzheimer’s disease?

Alzheimer’s is a neurodegenerative disease that develops progressively. It is caused by the development of plaque and tangles in brain cells.

Q- What are the significant risk factors of Alzheimer’s?

The significant risk factors include older age, genetics or family history, lifestyle factors, trauma, head injury, and insomnia etc. 

Q- Can Alzheimer’s development be prevented?

No, Alzheimer’s can’t be prevented. However, managing certain lifestyle factors can lower the risk of getting the disease. This includes regular physical exercise, intake of a nutrient-dense diet, quality sleep, managing chronic disorders, etc. 

Q- Can stem cell therapy cure Alzheimer’s?

Currently, there are no curative treatments available for Alzheimer’s. However, stem cell therapy can potentially alter disease trajectories through paracrine signaling.