Alzheimer’s Disease Cause: Emerging Regenerative Research

Alzheimer’s begins far before the memory begins to fade. The underlying biology begins long before the first noticeable changes. 

The disease develops through a complex interaction of multiple processes, including neuronal signals, immune response, surrounding cell interaction, vascular network, cellular communication, etc. Researchers reported abnormal amyloid-β protein interaction and tau tangles. Age-associated cellular changes, chronic neuronal inflammation, impaired mitochondrial function, oxidative stress, genetic susceptibility, or altered blood-brain barrier (BBB) influence neurodegeneration. 

Understanding Alzheimer’s Disease Causes requires focusing beyond single protein or pathway alteration. To understand the mechanism of Alzheimer’s development, researchers focus on unveiling multiple cellular or molecular pathway interactions. The current conventional therapeutics focus on symptom management. Regenerative medicine intends to regulate altered neuronal function. Stem Cell Therapy for Alzheimer’s is widely explored for its potential to boost regeneration and repair mechanisms. Regenerative research is still evolving. The important question is the context of stem cell therapy safety, survival, delivery, and long-term outcome. The current article explores the potential of introducing stem cell therapy while considering various Alzheimer’s disease causes. 

Ask The Expert

What are the Causes of Alzheimer’s Disease?

Alzheimer’s disease occurs due to multiple microscopic changes in the brain. The changes in the brain occur long before the signs of memory loss appear. Normally, there are 100 billion neurons in the brain connected in the form of a communication network. There is no definite cause of Alzheimer’s disease. This means that the root cause among individuals varies. Some of the explored causes include: 

Genetic or Age-Associated Changes

• Alzheimer’s is hereditary/genetic
• Individuals with a family history of Alzheimer’s possess a 10-30% higher risk of developing the disease
• APOEε4 gene increases risk of Alzheimer’s development  
• Increasing age triggers neuronal death and protein modification
• The buildup triggers chronic low-grade inflammation in the brain, leading to brain cell death or shrinkage

Amyloid Protein Buildup

• In the Alzheimer’s brain, amyloid protein sticks together, resulting in plaque formation
• Enzymes including beta-secretase and gamma-secretase cut out the amyloid plaque abruptly
• It creates beta-amyloid fragments (Aβ42) 
• It blocks electrical and chemical signals, triggering the lethal cascade

Tau Protein Tangles

• Tau protein normally stabilizes the microtubules that act as structural tracks inside neurons
• Hyperphosphorylation makes chemical changes that detach it from microtubules
• Formation of free tau protein sticks together inside neurons that forms neurofibrillary tangles
• Absence of tau support collapses adequate nutrient supply to the brain cells (leads to cell death) 

What Happens Inside Alzheimer’s Brain?

The Occurrence of Alzheimer’s Disease Causes Multiple Intrinsic Changes in the Brain:

• The neuronal damage leads to cellular communication loss
• Dysfunctional glial cells (triggered by A plaques and tau tangles) alter the brain microenvironment; they trigger immune responses
• Chronic low-grade inflammation triggers pro-inflammatory cytokine release (TNF-, IL-6, and IL-1)

*To combat the changes at the cellular and molecular level, researchers are actively exploring Stem Cell Therapy for Alzheimer’s. The intent is to support a healthier microenvironment and combat neurodegeneration

How is Alzheimer’s Treated?

There is no definite cure for Alzheimer’s. Alzheimer’s disease treatments are based on diagnosed complications and underlying causes. The conventional treatment involves:

Medication

• Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) block an enzyme that damages the brain
• Lecanemab or donanemab are monoclonal antibodies; they target the immune system and destroy amyloid protein-associated damage
• Lecanemab targets amyloid fibers; donanemab targets clumped amyloid protein
• NMDA antagonist, like memantine, blocks NMDA receptors that bind in the brain
• For symptom management, various medications, including antidepressants, antiseizure, antipsychotics, etc., are prescribed

Lifestyle Intervention

• Introduction of dietary intervention
• Regular physical activities increase adequate oxygen flow in the brain
• Mentally active games like board games, musical instruments, crossword puzzles, etc. 
• Maintain social connection

Behavioural Management

• Creation of a safe and supportive environment
• Keep everyday useful things in a defined space (medicines, wallets, phone, etc.)
• Activate location tracking on the phone
• Use calendar or whiteboards to track daily schedules
• Remove environmental clutter like excessive furniture, uneven flooring, rugs, etc. 

Why Do Conventional Approaches Lack Effective Management?

• Conventional Alzheimer’s disease treatment approaches primarily focus on symptom management
• Medications have narrow biological targets (specific pathological features); however, Alzheimer’s disease causes are multiple
• The control of disease pathways is difficult; Alzheimer’s is a progressive condition, and targeting one pathway isn’t sufficient to restore lost neuronal function
• There is an intense need for advanced strategies that can support neuronal survival, reduce neuroinflammation, modulate immune response, and create a supportive microenvironment

How is Regenerative Medicine Transforming the Alzheimer’s Treatment Landscape?

Researchers are widely exploring Stem Cell Treatment for Alzheimer’s as a regenerative approach. The latest breakthrough looks promising in targeting the problem at the cellular level. Currently, mesenchymal stem cells (MSCs) are widely explored due to their ability to transform into specific cell types and send out paracrine signalling. 

The Key Targets of Stem Cell Therapy for Alzheimer’s Include:

• Stimulate Tissue Repair: MSCs differentiate into different cell types, including neuron-like cells. They potentially replace the lost or damaged neurons. MSCs release various cytokines and signalling molecules that boost cell-to-cell communication. This boosts the body’s natural repair mechanism. This potentially aids in cognitive function restoration  
• Combat Neuroinflammation: MSCs release various anti-inflammatory cytokines that reduce inflammation. They actively combat low-grade chronic inflammation. Combating neuroinflammation slows down disease progression
• Immunomodulation: MSCs modulate immune response and create a calmer microenvironment around the brain cells. They minimize the risk of immune rejection. This supports the action of MSCs in inducing tissue repair and other conventional treatment approaches
• Combat Amyloid Plaque Buildup: MSCs potentially can reduce amyloid beta protein accumulation (major hallmark of Alzheimer’s). This can slow down Alzheimer’s disease progression and improve cognitive function [1]

*NOTE: Stem cell therapy for Alzheimer’s is at an early stage of development. The early studies indicate a positive trend. In future, the focus must be on the development of well-structured clinical trials to establish long-term treatment efficacy and safety. 

What Do the Early Research and Clinical Studies Indicate?

Preclinical and Clinical Studies Indicate a Positive Trend. The Key Indications Include:

• MSCs reduced the buildup of Aβ plaques in the brain and improved cognitive function
• MSCs potentially reduce neural inflammation, combat oxidative stress in the brain and create a calmer brain microenvironment [2]
• The stem cell type, quality, source, isolation procedure, and administration procedure affect the efficacy of the Alzheimer’s disease treatment

*Advancells, India, is a leading manufacturer and supplier of clinical-grade stem cells for chronic conditions including Alzheimer’s. The cell product is accompanied by a Certificate of Authentication (CoA) 

Key Takeaways

• There are multiple Alzheimer’s disease cause
• The current conventional Alzheimer’s treatment approach targets symptomatic management and not the root cause
• The emerging regenerative medicine in the form of stem cell therapy for Alzheimer’s appears promising
• Stem cells potentially target multiple cellular and molecular pathways simultaneously; they can combat the multifaceted nature of the Alzheimer disease development
• The future must focus on launching well-structured, large-scale clinical trials. This is crucial to establish the long-term efficacy and safety of the treatment.

References

1. Cao Z, Kong F, Ding J, Chen C, He F, Deng W. Promoting Alzheimer’s disease research and therapy with stem cell technology. Stem cell research & therapy. 2024 May 7;15(1):136. 
2. Hernández AE, García E. Mesenchymal stem cell therapy for Alzheimer’s disease. Stem Cells International. 2021;2021(1):7834421. 

FAQ’s

Q- What are the causes of Alzheimer’s?

Alzheimer’s disease causes a complex interaction of age, genetics, amyloid and tau pathology, neuroinflammation, vascular changes, and other biological factors. 

Q- Is stem cell therapy being studied for Alzheimer’s disease?

Yes. Stem cell therapy for Alzheimer’s is being investigated mainly for its potential to support neuronal survival, modulate inflammation, and influence the brain’s cellular environment. Much of the evidence remains at the preclinical or early clinical research stage.

Q- Can stem cell treatment cure Alzheimer’s disease?

There is currently no established stem cell treatment that can cure Alzheimer’s disease. Research is exploring whether regenerative approaches could address some of the cellular and biological changes associated with neurodegeneration.

Q- What regenerative research in Alzheimer’s targets?

Current research is exploring approaches that go beyond targeting individual disease markers, including neuroprotection, immune modulation, cellular signalling, and restoration of the neural microenvironment.