Stem Cells for Alzheimer’s Disease Treatment

About Alzheimer’s Disease (AD)

Alzheimer’s is a degenerative brain disorder that gradually impairs memory and other cognitive functions such as comprehension, language, attention, reasoning, and judgment. As the disease progresses, individuals lose the ability to perform basic daily tasks. Though Alzheimer’s itself is not directly fatal, it significantly increases the risk of secondary complications that can ultimately lead to death.

What are Preserved skills?

Research indicates that implicit memory skills often remain intact in patients with Alzheimer’s. These skills include tasks such as tying shoelaces, brushing teeth, typing, or playing an instrument. Implicit memory is an unconscious system distinct from explicit memory and cannot be voluntarily recalled. Instead, it manifests through improved performance based on past experiences. These preserved skills can play a crucial role in designing rehabilitation programs and maintaining functional independence in daily life.

Is Alzheimer’s disease the same as dementia?

No. Dementia is a broad clinical term describing symptoms such as memory loss, impaired thinking, and behavioral changes. Alzheimer's disease is a specific brain disease and the most common cause of dementia. The other causes of dementia include vascular dementia, Lewy body dementia, frontotemporal dementia, and others. While dementia is a clinical symptom, Alzheimer’s is the cause of the symptom.

What is the new Alzheimer’s treatment in 2025?

Recent advances have focused on monoclonal antibodies targeting beta-amyloid, aiming to modify disease progression while minimizing dosage and related side effects. There's also growing interest in targeting tau protein pathways. However, none of them can repair the neuronal damage, causing the patient to live with diminished cognitive skills.

In parallel to the current Alzheimer’s treatment options, research on stem cell therapy has also accelerated. Its regenerative effects on neural repair have shown favorable results in cognitive restoration.

Furthermore, research is tailoring stem cell therapy based on disease and patients' characteristics. This approach maximizes the benefits of the therapy, venturing into the field of personalized stem cell therapy for Alzheimer's disease.

Diagnosis

Alzheimer's disease diagnosis is a multi-faceted process that integrates clinical assessments and imaging. Together, these tools enable early diagnosis of Alzheimer's disease, allowing for timely intervention and better patient management.

Family History: Initially, a detailed review of the patient’s medical and family history provides important context, as genetic predisposition and previous health conditions may hint at the main cause of Alzheimer’s disease or the disease itself.

Cognitive Tests: Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) serve to evaluate memory, attention, language, and executive functions, helping to quantify the degree of cognitive impairment.

Blood Tests: Routine blood tests are performed to exclude other potential causes of dementia-like symptoms. These include complete blood counts (CBC), thyroid function tests (TSH), and vitamin B12 levels, among others. These help rule out reversible conditions such as thyroid disorders or nutritional deficiencies.

Brain Imaging: Magnetic resonance imaging (MRI) and computed tomography (CT) scans are used to detect structural abnormalities such as brain shrinkage and enlarged ventricles that are characteristic of Alzheimer's. Volumetric MRI can track brain volume changes over time, specifically monitoring the hippocampus, a critical region for memory that typically atrophies in Alzheimer’s. Advanced imaging modalities such as positron emission tomography (PET), functional MRI (fMRI), and single-photon emission computed tomography (SPECT) provide insights into metabolic activity and brain function.

Biomarkers: Cerebrospinal fluid (CSF) collected via lumbar puncture can be analyzed for levels of beta-amyloid 42, phosphorylated tau, and total tau proteins. In Alzheimer's, CSF beta-amyloid 42 tends to be decreased, reflecting its deposition in plaques, while tau proteins increase, indicating neuron damage.

Recent breakthroughs have introduced blood-based biomarker tests for Alzheimer’s disease diagnosis that detect amyloid and tau proteins at very low concentrations, making diagnosis less invasive and more accessible. For instance, the FDA-cleared Lumipulse test measures the ratio of plasma phosphorylated tau to beta-amyloid to predict disease presence with high accuracy.

Early Signs & Symptoms of Alzheimer’s Disease (AD)

The neural damage in the disease manifests clinically as the following common symptoms of Alzheimer’s disease.

Memory: Memory loss, particularly short-term memory impairment, is a hallmark symptom of Alzheimer's disease and distinguishes it from normal forgetfulness. In Alzheimer's, the memory loss is persistent and worsens over time, significantly disrupting daily functioning. Patients often repeat statements or questions because they forget recent conversations. As the disease progresses, patients can lose the ability to recognize familiar places or people, indicating deeper cognitive decline. Moreover, difficulties in expressing themselves become apparent as patients struggle to find the right words and have trouble retaining new information, which affects their overall communication.

Cognition: Patients experience trouble concentrating and thinking clearly, making multitasking especially difficult. Simple everyday activities that involve planning or coordination—such as driving, cooking, managing finances, or shopping—become increasingly challenging. Their judgment weakens, which may lead to poor decision-making. Over time, the cognitive decline worsens to the point where individuals may forget how to perform basic tasks such as dressing, bathing, or using the toilet, signaling a loss of independence.

Behavior: The changes in memory and cognition have significant effects on patients' behavior and mood. Emotional symptoms such as depression and mood swings are common, often accompanied by restlessness, aggression, and sleep disturbances. Patients may withdraw socially, become paranoid or delusional, and sometimes wander, creating additional challenges for caregivers and loved ones. Behavioral changes are part of the broader neuropsychiatric symptoms that emerge as the disease advances.

Alzheimer’s symptoms begin gradually but worsen steadily over time. As the disease progresses, patients may have difficulty performing familiar tasks and show signs of involuntary muscle contractions and abnormal postures. Later stages are often marked by bladder and bowel incontinence, forcing patients to rely heavily on caregivers for all aspects of daily living. The progressive nature of Alzheimer's disease leads to increasing dependence, requiring comprehensive support as cognition, memory, and physical functions decline. This gradual but relentless deterioration underlines the serious impact of Alzheimer’s on both patients and their families.

Available Types of Alzheimer’s Disease (AD)

Different types of Alzheimer’s disease are categorized based on age of onset and clinical presentation:

Late-Onset Alzheimer’s Disease (LOAD): is the most common form and typically begins manifesting after the age of 65. This form is generally characterized by a slow but progressive decline in cognitive functions such as memory, reasoning, and decision-making.

Early-Onset Alzheimer’s Disease (EOAD): It occurs before the age of 65 and is far less common. It is often diagnosed later because its symptoms can be atypical or confused with other conditions, and it tends to follow a more aggressive course, progressing faster than LOAD.

Atypical Subtype: It differs not only in terms of age of onset but also brain pathology and symptoms. These atypical forms tend to affect younger individuals and often present with dysfunctions outside the usual memory impairment, such as difficulty with vision, language, motor skills, or behavioral regulation.

Researchers are also identifying cellular subtypes that may influence treatment response and disease progression.

Stage 1: Pre-clinical or the Pre-symptomatic stage

At this stage, early pathological changes begin occurring in the brain structures critical for memory and cognition, such as the cortex and hippocampus. However, there are no noticeable symptoms or impairment in daily functioning. This stage can remain undetected for years or even decades.

Stage 2: Mild or Early Stage

Patients start experiencing early symptoms of Alzheimer’s disease, including mild memory loss, difficulties in concentration, occasional disorientation about time and place, and mood changes like depression or anxiety. Despite these symptoms, individuals in this stage are typically still capable of living independently.

Stage 3: Moderate Stage

As the disease advances into the moderate stage, the damage spreads more extensively to the cerebral cortex, resulting in more severe memory loss, difficulty recognizing close family and friends, impaired communication skills, and a loss of impulse control. At this point, people require increasing assistance with everyday tasks such as reading, writing, and managing personal care.

Stage 4: Severe AD or Late-stage

The disease has spread throughout the entire cerebral cortex, and patients lose the ability to recognize loved ones completely. Late-stage symptoms of Alzheimer’s disease include declining visuospatial abilities, which cause difficulties in navigation and orientation, making them entirely dependent on caregivers for all daily living activities.

Understanding the distinctions among these Alzheimer’s categories and the progression through its stages is crucial for diagnosis, care planning, and research into therapeutic interventions.

What Causes Alzheimer’s Disease (AD)?

Alzheimer’s disease is a multifactorial disorder, arising from a combination of biological, genetic, and environmental factors. It occurs due to the death of nerve cells, particularly in the hippocampus region of the brain. Here’s a more detailed breakdown of the causes of Alzheimer’s disease:

• Protein Accumulation: It is the leading cause of Alzheimer’s disease, involving amyloid and tau proteins.
• Amyloid Plaques: Amyloid plaques are formed by clumps of beta-amyloid proteins, specifically the toxic form called amyloid-beta 42 (Aβ42). These proteins are fragments from a larger protein called amyloid precursor protein (APP). Normally, Aβ is cleared by the brain, but in Alzheimer's disease, this clearance fails, allowing Aβ to accumulate between neurons, disrupting communication between neurons and triggering immune responses that lead to inflammation and nerve cell death.
• Neurofibrillary Tangles: Inside neurons, tau protein normally helps in transporting nutrients and molecules. In Alzheimer’s, tau undergoes hyperphosphorylation, causing its aggregation into twisted thread-like structures called neurofibrillary tangles. These tangles block nutrient and molecule transport inside neurons, impair synaptic communication, and lead to neuronal dysfunction and degeneration.
• Genetic Mutations: Mutations in genes such as APP, PSEN1, and PSEN2 contribute to the genetic causes of Alzheimer’s disease. These mutations increase the production or aggregation of beta-amyloid, accelerating plaque formation. Moreover, the APOE ε4 allele is a strong genetic risk factor. It influences cholesterol metabolism and impairs the brain’s ability to clear beta-amyloid, promoting its accumulation.

In addition to the Alzheimer’s disease causes, several factors increase the susceptibility to Alzheimer’s.

• Age: The single most significant risk factor is age. Alzheimer’s prevalence roughly doubles every five years after age 65, making advancing age the primary contributor.
• Environment: Exposure to air pollution, certain metals, infections, and poor diet may generate oxidative stress and inflammation, increasing Alzheimer's risk.
• Cardiovascular Health: Heart failure or poor heart function reduces blood flow to the brain, causing hypoxia (low oxygen) and neural injury, which can promote dementia.
• Obesity & Diabetes: High blood sugar and insulin resistance in diabetes promote beta-amyloid accumulation and brain inflammation. Obesity adds to risk by releasing inflammatory cytokines that exacerbate insulin resistance and damage.
• Other Factors: Traumatic brain injury, cerebrovascular disease, smoking, high homocysteine levels, and higher parental age at birth also increase Alzheimer’s susceptibility.

Stem Cells for Alzheimer's Disease (AD) Treatments

Current treatments for Alzheimer's disease often follow the "one drug, one mechanism" approach. They target specific pathological features such as amyloid-beta plaques, tau protein tangles, or neuroinflammation. However, Alzheimer's is an extremely complex disease involving multiple interrelated pathological processes, making treatment by focusing on a single pathway unlikely to achieve significant clinical success. Combination therapy can address this complexity but even they fail to regenerate neurons.

Stem cell therapy for Alzheimer’s disease stands out as a unique treatment approach because it has the potential to target several key pathological mechanisms of Alzheimer's simultaneously, offering a multi-faceted therapeutic effect. The research has revealed that the stem cells can treat the disorder in the following ways:

• They reduce the size of amyloid-beta plaques by regulating the levels of amyloid precursor protein and its processing enzymes. These cells also activate microglial cells, promoting plaque clearance.
• They also induce neural progenitor differentiation into mature neurons via the Wnt signaling pathway. Stem cells can differentiate into neural cells to replenish the lost neurons
• They switch brain immune cells into anti-inflammatory phenotypes by secreting indoleamine-2,3 dioxygenase (IDO), TGF-β, and prostaglandins.
• Stem cells protect neural cells from toxic protein buildup, and the resulting oxidative stress and inflammation.
• Mesenchymal stem cells derived from an umbilical cord secrete galectin-3, decreasing the neurotoxicity resulting from Aβ-42 accumulation.
• They also promote neural connectivity and improve blood supply.
• These cells increase IL-10 levels that suppress neuroinflammation.

Together, these effects lead to improvements in cognition and behavior. Clinical trials with allogeneic MSC therapies have shown encouraging results, highlighting the potential of Alzheimer’s stem cell treatment to address multiple disease pathways simultaneously, unlike conventional single-target drugs. This multi-mechanism approach may be key to more effective Alzheimer's disease treatment by stem cell therapy in the future.

Frequently Asked Questions

Q1. How close is stem cell therapy to curing Alzheimer’s disease?

Stem cell therapy represents a highly promising treatment approach. It targets brain inflammation and plaque accumulation, which are key contributors to Alzheimer’s pathology. Unlike conventional treatments that primarily aim to slow cognitive decline, stem cell therapy advances further by promoting neuronal regeneration. This reparative potential enhances cognitive function rather than merely delaying deterioration. Although stem cell therapy offers numerous advantages, it is not yet classified as a definitive cure—but it remains the closest therapeutic strategy to achieving one.

Q2. How much is the cost of stem cell therapy for Alzheimer’s disease?

The cost of stem cell therapy varies significantly based on the type of stem cells used, the medical facility or research center, and the geographic region. Moreover, the total expense can rise depending on the number of infusions required throughout the treatment course. Compared to Western countries, the cost of stem cell therapy for Alzheimer’s disease in India is considerably lower. The affordable prices, advanced medical infrastructure, and skilled clinical expertise has encouraged international patients to seek stem cell treatment for Alzheimer’s in India.

Q3. How many stem cell infusions for Alzheimer’s disease treatment are needed?

The number of stem cell infusions varies depending on the patient’s age, stage of disease, and other comorbidities. Therefore, a thorough medical evaluation, consultation with a qualified clinician, and monitoring of post-treatment progress are essential to accurately determine the appropriate number of stem cell sessions for each individual.

Q4. Is stem cell treatment for Alzheimer’s disease safe?

Clinical trials prefer human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) for stem cell therapy for Alzheimer’s disease. These cells carry a low risk of immune rejection and high regenerative potential. Current studies involving UCB-MSCs have not identified any significant side effects, reinforcing their potential as a safe therapeutic option.