Understanding Degenerative Diseases: causes, symptoms and prevention

Degenerative diseases are a growing concern for global health, affecting millions of people and having a significant impact on patients’ quality of life.

These conditions are characterized by the progressive deterioration of organ and tissue functions, often associated with aging but can arise at any stage of life.

In today’s context, where increasing longevity and health challenges are becoming more evident, understanding degenerative diseases is essential. With nearly 17 million premature deaths related to degenerative diseases each year (1), it is crucial to deepen our knowledge about these conditions.

In this article, we will explore the main types of degenerative diseases, their causes, symptoms, and how we can act to prevent them. 

What is a Degenerative Disease?  

A degenerative disease is a condition characterized by the progressive and irreversible deterioration of cells, tissues, and organs. This degradation occurs over time and can result in loss of function, disability, or cell death (2). These diseases frequently affect the central nervous system and the musculoskeletal system, among other vital systems.

Degenerative diseases can be classified according to the affected tissue or organ, such as (3):  

• Neurodegenerative Diseases: A group of complex diseases characterized by neuronal loss and the progressive degeneration of different areas of the nervous system.
• Musculoskeletal Degenerative Diseases: Diseases that generally cause degeneration of the joints, cartilage, and bone structures, leading to pain, inflammation, stiffness, or loss of mobility.
• Cardiovascular Degenerative Diseases: Conditions in which there is a progressive accumulation of atheromatous plaques in the arteries, leading to reduced blood flow and increasing the risk of events such as heart attacks and strokes.

Definition and Impact of Chronic Degenerative Diseases  

Chronic degenerative diseases (CDD) are non-infectious, slow-progressing, long-term conditions, such as diabetes, heart disease, obesity, chronic respiratory diseases, neurodegenerative diseases and cancer.

These conditions generally result from a combination of multiple factors leading to the progressive deterioration of health. Their pathogenesis is complex and involves the interaction of known behavioral, environmental, and genetic factors (4).

CDD have been the most frequent causes of long-term disability and death worldwide. Globally, more than 30% of the population is affected by one or more chronic degenerative diseases, and 70% of public health resources are allocated to these conditions (5).

According to recent projections, chronic degenerative diseases will account for 80% of all diseases worldwide by 2030, representing a significant threat to human health (6).

These diseases are primarily represented by conditions such as: 

• Obesity;
• Cardiovascular Diseases (CVD);
• Diabetes;
• Chronic Kidney Disease (CKD);
• Inflammatory Bowel Diseases;
• Osteoporosis;
• Sarcopenia;
• Huntington’s Disease; 
• Rheumatoid Arthritis; 
• Chronic Respiratory Diseases;
• Cancer. 

They have been the most frequent causes of prolonged disability and death worldwide (1).  

What is the Difference Between Chronic and Degenerative Diseases?  

The difference lies mainly in the mechanisms and characteristics of disease progression. 

• Chronic Diseases: These are health conditions that persist for a long period, generally more than three months, and often for a lifetime. They can be managed but rarely cured, such as hypertension, diabetes, asthma, rheumatoid arthritis, and heart disease.
• Degenerative Diseases: These are a subtype of chronic diseases, characterized by the progressive deterioration of cells, tissues, or organs over time. The term “degenerative” refers to the process of degradation or loss of function (2), such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and osteoarthritis.  

Therefore, chronic disease is a broader term encompassing any persistent and long-lasting health condition, while degenerative disease is a specific type of chronic disease involving the progressive deterioration of cell, tissue, or organ function. 

It is important to note that while all degenerative diseases are chronic, not all chronic diseases are degenerative.  

What Are the Main Risk Factors Associated with Degenerative Diseases? 

 Degenerative diseases have multiple causes and risk factors that can vary depending on the specific type of disease. However, the main causes and risk factors associated are:  

• Genetic Factors: Presence of variants in specific genes, positive family history, and epigenetic modifications.
• Lifestyle: According to the WHO, smoking, poor diet, lack of physical activity, and excessive alcohol consumption are significant risk factors contributing to most deaths related to these conditions.
• Aging: This is the primary risk factor for degenerative diseases, especially neurodegenerative diseases like Alzheimer’s and Parkinson’s, where the risk of development increases with age (7) . Studies have revealed that the brain tissue of older individuals contains abnormal deposits of aggregated proteins, such as hyperphosphorylated Tau (p-tau), β-amyloid (Aβ), and α-synuclein; however, it is still unclear whether these deposits are related to the degree of cognitive impairment (8).
• Exposure to Toxins: Heavy metals, pesticides, industrial solvents, and pollutants can generate reactive oxygen species (ROS). These molecules cause oxidative stress, leading to cell injury and death, especially of nerve cells. Additionally, toxins can interfere with mitochondrial function, reducing ATP production and leading to cell degeneration.
• Autoimmune Processes: The immune system mistakenly attacks healthy cells and tissues, which can damage neurons, synapses, joints, and other tissues, leading to progressive degeneration.
• Chronic Inflammation: Results in the continuous release of pro-inflammatory cytokines, enzymes, and other molecules that can damage cells and tissues over time and accelerate the degenerative process. Additionally, the accumulation of abnormal proteins and cellular vulnerability can lead to cell death and, consequently, to the degeneration of affected tissues. 

What Are the Main Degenerative Diseases and Their Characteristics? 

Among the main degenerative diseases, we can mention: 

Alzheimer’s Disease (AD)  

It is the most common form of neurodegenerative disease and the leading cause of dementia, representing 60-80% of cases. This condition is characterized by neuronal loss and cognitive dysfunction and is rapidly becoming one of the most costly, deadly, and burdensome diseases of the century (9).  

In 2018, Alzheimer’s Disease International estimated that around 50 million people worldwide were living with dementia, a number expected to triple by 2050 (10).

Alzheimer’s disease affects memory and other cognitive functions. It can manifest in two main forms: early onset, associated with dominant genetic variants in three specific genes (APP, PSEN1, and PSEN2), causing symptoms before age 65 (11, 12); and late onset, being the most common type occurring later in life, usually without a single identified genetic cause, and is sporadic (13).

The disease is characterized by the accumulation of abnormal proteins in the brain, such as β-amyloid and neurofibrillary tangles formed by Tau protein. These deposits cause the gradual loss of synapses and neuronal death, resulting in cognitive function deterioration. However, the exact causes and mechanisms driving the progression of the disease are not yet fully understood (12, 14). 

The main risk factors for Alzheimer’s disease include advanced age (over 65 years), presence of at least one E4 allele in the APOE gene (15), inadequate diet, lack of physical exercise, and associated comorbidities such as diabetes, stress, and cerebrovascular disease (16, 17). Additionally, women are more prone to developing Alzheimer’s, especially after age 80 (10).  

Parkinson’s Disease (PD)  

It is a chronic and progressive neurodegenerative disorder that primarily affects older adults, although it can also appear in younger patients. It is the second most common neurodegenerative disease (18), affecting about 4 million people worldwide, according to the World Health Organization.

PD results from the degeneration of dopaminergic neurons in the substantia nigra of the midbrain and the formation of Lewy bodies, which are abnormal intracellular aggregates composed of various proteins that impair optimal neuronal function (19, 20).

The symptoms of Parkinson’s disease include motor and non-motor manifestations. Patients generally present with resting tremor, rigidity, bradykinesia (decreased speed and amplitude of movements), and stooped posture with loss of balance. Additionally, the disease may be associated with neurobehavioral disorders (such as depression and anxiety), cognitive impairment (dementia), and autonomic dysfunctions, including orthostatic hypotension, hyperhidrosis, constipation, and pain (19).

Most cases have a multifactorial origin, involving a combination of environmental and genetic factors (21). The main risk factors include age, with the average onset age between 50 and 60 years, family history, specific genetic variants (responsible for 5-10% of cases), and exposure to pesticides.  

Multiple Sclerosis (MS)

It is the most common non-traumatic disabling disease affecting young adults. It is a chronic, predominantly immune-mediated, and degenerative condition that affects the central nervous system, including the brain and spinal cord (22). The disease affects about 2.5 million people worldwide, with women being the most susceptible.

In multiple sclerosis, the immune system attacks the myelin, the protective layer around nerves in the brain and spinal cord due to inflammation. This damage to the myelin interferes with communication between the brain and the rest of the body, causing delayed or blocked nerve signals, which can lead to a variety of neurological symptoms and impact quality of life and functional capacity (23).

MS is a complex and multifactorial disease with various risk factors involved. Among genetic factors, mutations in several genes increase susceptibility to the disease, while well-defined environmental factors such as vitamin D deficiency, exposure to ultraviolet B (UVB) light, Epstein-Barr virus infection (causing mononucleosis), obesity, and smoking also play significant roles (24).

The symptoms of multiple sclerosis can vary widely in type and severity, affecting the motor, sensory, visual, and autonomic systems (25). Disease progression is unpredictable: some individuals experience mild and sporadic symptoms, while others face more severe and progressive forms.

The most characteristic symptoms include fatigue, optic neuritis (inflammation of the optic nerve), double or blurred vision, symptom fluctuations with increased body temperature, abnormal sensations of electric shock or tingling when bending the neck, muscle spasms, and mobility difficulties (25, 26).

Relapses in MS occur due to focal areas of demyelination that evolve over 24 hours and may persist for days or weeks before generally improving, though not exclusively (27). 

Amyotrophic Lateral Sclerosis (ALS)

ALS is a rare and progressive neurodegenerative disease characterized by dysfunction of both upper and lower motor neurons, which control voluntary muscles (28). Due to the inability to send signals to the muscles, patients suffer from progressive weakness of voluntary skeletal muscles, affecting limb movement, swallowing (dysphagia), speech (dysarthria), and respiratory function. This leads to atrophy, paralysis, and eventually early death. 

Clinical weakness in ALS typically spreads contralaterally, rostrally, and caudally, often following anatomically contiguous progression. Recent research has revealed that 85% of amyotrophic lateral sclerosis (ALS) patients exhibit a focal onset in one body segment, which then spreads to the contralateral side and subsequently to adjacent anatomical segments (29). 

ALS can manifest in various phenotypes, with the most common being bulbar onset and spinal onset (cervical and lumbar), representing about one-quarter to one-third of cases. Other phenotypes include flaccid arm and leg, primary lateral sclerosis, progressive muscular atrophy, respiratory onset, and hemiplegic presentations (30, 31). 

Factors such as age (with higher prevalence between 55 and 75 years), sex (with increased risk for females), and genetics influence these phenotypes, and there are variations among different populations (32, 33). The recent recognition of phenotypic heterogeneity and ALS as a complex syndrome, often associated with behavioral deficits, may help doctors diagnose the disease earlier (28). 

Early diagnosis is crucial for symptom management and improving the quality of life for patients, as there is currently no cure for ALS. 

Osteoporosis

Osteoporosis is characterized by low bone mass and microstructural deterioration of bone tissue, which increases bone fragility and raises the risk of fractures (34). In 1994, the World Health Organization (WHO) established criteria for measuring bone mineral density (BMD) based on reduced bone strength or density. These criteria allow for the diagnosis of osteoporosis before fractures occur, identifying individuals at high risk (35).

Although bone density is an important factor, it is only one of many aspects to consider, as age, life expectancy, bone loss, and bone renewal also play significant roles (36). Osteoporosis is especially common in postmenopausal women.

It is estimated that 50% of women and 20% of men over 50 will experience an osteoporosis-related fracture at some point in their lives (37).

The most common treatment includes vitamin D and calcium supplementation, which has been shown to be effective in reducing fracture risk in bone preservation studies (38). Like other degenerative diseases, osteoporosis tends to worsen over time, especially if not properly managed. 

How to Prevent Degenerative Diseases? 

To prevent degenerative diseases, it is essential to adopt a healthy lifestyle, including a balanced diet, regular physical exercise, and maintaining a healthy weight. Consuming foods rich in calcium and vitamin D helps protect bones and joints, while omega-3 intake—previously highlighted here on the blog—is important for preventing cardiovascular and chronic diseases, contributing to brain health and reducing inflammation. 

Additionally, incorporating antioxidant therapies has been effective in preventing neurodegenerative diseases. It is equally important to avoid risk factors such as smoking and excessive alcohol consumption. 

SYNLAB and Tests for Investigating Degenerative Diseases

SYNLAB offers a range of tests for investigating major degenerative diseases, including:

Light Chain Neurofilament Assessment 

The neurofilament assessment is used as a biomarker for neurodegenerative or demyelinating conditions such as ALS, Alzheimer’s, Parkinson’s, and Multiple Sclerosis; or for conditions potentially associated with axonal injury. The test can be performed on cerebrospinal fluid (CSF) samples, being particularly useful for early investigation and diagnosis of multiple sclerosis, ALS, and severe neurological conditions; or on serum samples, suitable for continuous and large-scale monitoring of neurodegenerative disease progression and treatment response. 

Adgen Test 

The Adgen test is a next-generation sequencing (NGS) panel that analyzes gene variants in APP, PSEN1, PSEN2, APOE and A2M, allowing for the investigation of genetic predisposition to Alzheimer’s disease, facilitating early diagnosis. 

APOE Genotyping 

This test performs genotyping of the APOE gene using qPCR technology and assesses the presence of the risk allele for Alzheimer’s disease. 

Beta-Amyloid/TAU Protein, CSF 

This test evaluates biomarkers associated with neurodegenerative diseases, specifically focusing on Alzheimer’s disease. It includes the analysis of proteins such as beta-amyloid Aβ1-42 and Aβ42/40, as well as biomarkers related to neurofibrillary tangles, such as total Tau (t-tau) and phosphorylated Tau (p-tau), in cerebrospinal fluid (CSF). 

Genetic Panel for Parkinson’s Disease 

A next-generation sequencing (NGS) panel assessing 18 genes related to Parkinson’s disease. It is generally indicated for researching gene variants, cases with a family history of Parkinson’s, and guidance on treatment and prognosis. 

Genetic Panel for Early-Onset Parkinson’s Disease 

A next-generation sequencing (NGS) panel assessing four genes related to early-onset Parkinson’s disease. Indicated for individuals with symptoms of Parkinson’s before age 50. 

Amyotrophic Lateral Sclerosis · C9orf72 

Genetic test assessing the presence of expansions in the C9orf72 gene, related to Amyotrophic Lateral Sclerosis. Indicated for patients presenting ALS symptoms, as hexanucleotide repeat expansions in the C9orf72 gene are one of the most common genetic causes of this condition.

NGS Panel for Amyotrophic Lateral Sclerosis 

A next-generation sequencing (NGS) panel assessing 31 genes related to Amyotrophic Lateral Sclerosis. A more comprehensive analysis, it may be indicated in situations where a more detailed diagnosis is needed or when investigating multiple genetic possibilities simultaneously, such as in cases with atypical symptoms and complex family history. 

Get to Know the SYNLAB Group, a Leader in Medical Diagnostic Services!

Performing accurate and up-to-date tests is essential for more precise diagnoses and better treatment direction. SYNLAB is here to help. 

We offer diagnostic solutions with strict quality control to the companies, patients, and doctors we serve. We have been operating in Brazil for over 10 years, are present in 36 countries across three continents, and are leaders in service provision in Europe. 

Contact the SYNLAB team to learn about the available tests. 

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