Alzheimer’s Disease Causes, Regenerative Medicine and New Research

Alzheimer’s disease is often recognised by its effect on memory, but the changes behind this condition begin much earlier and involve far more than forgetting familiar names or places. Gradually, the brain undergoes several biological changes that affect how nerve cells communicate, function, and survive. The buildup of amyloid-beta plaques, abnormal tau proteins, inflammation, and oxidative stress all contribute to this process. While these factors help explain Alzheimer’s Disease Causes, researchers are still working to understand how these mechanisms interact and influence disease progression.

Currently, conventional Alzheimer’s disease treatments intend to combat the symptoms, but they do not act at the cellular level. Researchers are exploring regenerative medicine as a new avenue of research. It focuses on protecting neurons and supporting the brain’s cellular environment. Stem cell therapy for Alzheimer’s potentially regulates inflammation, supports neuronal survival, and influences cellular repair mechanisms. The current article expands knowledge on Alzheimer’s disease causes, the available treatments, and growing evidence for regenerative medicine in therapeutic use. 

Ask The Expert

Alzheimer’s Disease Causes: What Happens Inside the Brain?

The exact Alzheimer’s Disease Causes is not well understood. It is thought to develop due to abnormal buildup of the proteins around the brain cells. The two majorly reported protein dysfunctions include:

• Amyloid Protein: Abnormal processing of the amyloid precursor protein (APP) leads to clump formation outside the nerve cells. This leads to bulky deposits called amyloid plaques. This leads to disruption of the communication between brain cells
• Tau Protein: The protein is responsible for stabilization of the microtubules and transport of nutrients inside the axon. The change occurs intracellularly, where the tau protein undergoes chemical changes. For instance, tau hyperphosphorylation detaches it from the microtubules, causing it to clump together and form neurofibrillary tangles. Such changes collapse the internal transport system and lead to neuronal death

The Alteration of the Protein Function Leads To:

• Disruption of the blood-brain barrier (BBB) and alteration of the brain microenvironment
• Microglial activation along with persistent neuroinflammatory responses
• Loss of synaptic plasticity and neuronal resilience
• Impaired cellular clearance mechanisms and protein homeostasis
• Synaptic dysfunction, neuronal damage, and progressive brain atrophy

What are the Key Cognitive & Behavioural Changes?

The Key Cognitive and Behavioral Changes Appear As:

• Early/ Mild Stage: Frequent memory lapses, difficulty in finding the right words, difficulty in expressing feelings, problems with handling or planning certain tasks
• Moderate Stage: Confusion occurs frequently, lose track or get lost in familiar places, mood shifts or changes in personality, partial loss of independence 
• Late / Severe Stage: Complete loss of communication ability, delayed or no response to the environment, complete loss of independence in performing everyday abilities, require assistance 24*7

Rethinking Alzheimer’s Disease Treatment: Why Targeting a Single Mechanism May Not Be Enough

Alzheimer’s treatment involves assessment of the patient’s condition and recommending suitable treatment options. Currently, Alzheimer’s disease has no cure. The current treatment focuses on symptom management, slows down neurodegeneration, and improves the patient’s quality of life. Alzheimer’s disease treatment involves:

Medication

• Cholinesterase inhibitors (donepezil, rivastigmine, galantamine). They block enzymes contributing to brain function decline
• Lecanemab and donanemab monoclonal antibodies IV infusion. Lecanemab targets amyloid fibers, and donanemab targets amyloid proteins
• NMDA antagonists (Memantine) block NMDA receptors and prevent glutamate binding. It slows neuronal degeneration
• Medication for comorbid condition management like antidepressants, antipsychotics, antiseizures, etc. These medications manage other factors

Physical Support

• Introduction of a physiotherapist to improve muscle strength and maintain muscle flexibilities
• Occupational therapist to support the patient with everyday activities
• Speech therapist to enable the patient to communicate
• Introduction of certain activities like board games, crosswords, puzzles, and musical instruments that challenge the brain to learn new skills

Dietary intervention

• Involvement of a dietician to maintain the patient’s specific nutritional needs
• Follow a balanced diet plan that involves a combination of fibers, proteins, carbohydrates, and fat

*NOTE: The above-mentioned Alzheimer’s disease treatment targets symptom management and tends to slow disease progression. However, none of the approaches intend to reverse the neurological changes in Alzheimer’s brain. Currently, researchers are widely exploring regenerative medicine that can target Alzheimer’s brain alterations at the cellular level.

Regenerative Medicine for Alzheimer’s: Exploring the Brain’s Capacity for Repair

Regenerative medicine targeting Alzheimer’s brains intends to restore the damaged neurons. Researchers are widely exploring Stem Cell Therapy for Alzheimer’s to support neuronal rejuvenation and boost repair mechanisms. Currently, applications of mesenchymal stem cells (MSCs) are widely used. MSCs are specialized cells that have both regenerative potential and send out paracrine signalling. The key mechanisms include:

Tissue Repair and Rejuvenation

• MSCs potentially differentiate into naive neuronal cells based on the stimulation
• They release various signalling molecules that boost cellular communication and support repair mechanisms

Anti-Inflammation and Immunomodulation

• MSCs release various anti-inflammatory cytokines; they combat the impact of pro-inflammatory molecules
• Stem cells modulate the immune response and create a calmer microenvironment. They support the survival of the surrounding neuronal cells

Reduced Amyloid Plaque Buildup

• MSCs potentially reduce accumulation of amyloid buildup
• They slow down the disease progression and support cognitive function

Minimal Immune Rejection Risk

• MSCs have lower immunogenicity; that is, they are less likely to have immune rejection
• Introduction of stem cell therapy for Alzheimer’s serves as a safe and viable option for Alzheimer’s brain [1]

What Does the Current Research Reflect?

Preclinical and early clinical studies have set a positive trend in the application of Stem Cell Treatment for Alzheimer’s. The clinical studies have shown a positive impact on the use of MSCs derived from umbilical cord blood cells. The key benefits include: 

• Safety and tolerability of the MSCs among Alzheimer’s patients 
• Improved memory function and cognitive abilities
• Neuronal regeneration with stimulation of neuronal regeneration. The early clinical studies reported improved brain function among Alzheimer’s patients
• Replacement of the damaged cells with healthy cells, potential functional recovery
• Anti-inflammation and creation of a supportive neuronal microenvironment [1, 2]

*NOTE: Currently, stem cell therapy for Alzheimer’s is at an early stage of therapeutic application. The outcome depends on various factors, including stem cell quality, source, isolation procedure, and administration. The treatment suitability depends on individual factors. It is crucial to consult renowned clinics and experienced clinicians and set realistic expectations before opting for a regenerative approach. Advancells, India, is a leading manufacturer and supplier of clinical-grade stem cells for neurodegenerative conditions, including Alzheimer’s. The products come with a Certificate of Authentication (CoA). 

Key Takeaways: Towards a New Research Paradigm 

• Alzheimer’s is a progressive neurodegenerative condition
• The current Alzheimer’s disease treatment focuses on symptom control based on Alzheimer’s Disease Causes
• Regenerative medicine with stem cell therapy for Alzheimer’s is evolving at a rapid pace
• Currently, clinicians are combining conventional treatment procedures with stem cell therapy to achieve improved outcomes 
• The treatment suitability depends on individual factors
• Future research focuses on developing well-structured, large-scale clinical trials (considering multiple indications) to establish long-term assessment outcomes

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. Karvelas N, Bennett S, Politis G, Kouris NI, Kole C. Advances in stem cell therapy in Alzheimer’s disease: a comprehensive clinical trial review. Stem Cell Investigation. 2022 Feb 21;9:2. 

FAQ’s

Q- What are the major causes of Alzheimer’s disease?

Alzheimer’s Disease Causes develops through a combination of biological and environmental factors. The accumulation of amyloid-beta plaques and abnormal tau proteins plays a major role in neuronal damage. Ageing, genetic susceptibility, neuroinflammation and metabolic changes can also influence disease development.

Q- Can stem cell therapy help in Alzheimer’s disease?

Stem cell therapy is being investigated for its potential to protect neurons, regulate inflammation and support the brain’s cellular environment. Early research has shown encouraging findings, particularly in experimental models, but its effectiveness in treating Alzheimer’s disease in humans remains under investigation.

Q- How does stem cell treatment for Alzheimer’s work?

Researchers are exploring how stem cells can influence damaged brain tissue through the release of growth factors, cytokines and other bioactive molecules. These signals may support neuronal survival, modulate inflammatory responses and help maintain synaptic function. The exact mechanisms and clinical benefits remain under investigation.

Q- Are exosomes studied for their potential for Alzheimer’s disease?

Yes, exosomes are small extracellular vesicles that carry proteins, lipids and genetic material involved in cell-to-cell communication. Researchers are investigating their potential role in neuroprotection, inflammation regulation and neuronal function, making them an interesting area of cell-free regenerative medicine research.

Q- Is regenerative medicine an established Alzheimer’s disease treatment?

No, regenerative medicine is evolving as a promising therapeutic approach for Alzheimer’s disease. Currently, researchers primarily focus on understanding their biological effects, safety and potential clinical applications. Established medical care remains essential for managing the condition.