Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, Amyotrophic lateral sclerosis, and multiple sclerosis are characterized by the progressive loss of neurons in specific regions within the brain or spinal cord. These illnesses are mostly associated with aging but can also manifest in younger individuals with genetic mutations and environmental factors playing a critical role in disease risk.

Several studies have shown that infections can cause and accelerate neurodegeneration.

In this article, we’ll explore how recurrent infections pave the way for neurodegenerative diseases, and what can be done to reduce the risk of dementia caused by infections.

What are Neurodegenerative Diseases?

Neurodegenerative diseases are a group of chronic, debilitating disorders that affect the nervous system, leading to the progressive death of neurons.

Symptoms of these diseases may vary depending on the region of the brain affected, including memory loss, tremors, muscle stiffness, paralysis, and eventually, death. Unfortunately, there is no cure for most neurodegenerative diseases, and treatments can only help alleviate their symptoms.

In recent years, many studies have suggested that neuroinflammation, oxidative stress, and protein aggregation play a critical role in the onset and progression of these diseases.

These events are mediated by immune cells such as microglia, astrocytes, and T cells, which respond to inflammation, toxins, and pathogens.

How Infections Promote Neurodegeneration

Infections are known to trigger inflammatory responses, whether caused by viruses, bacteria, fungi, or parasites.

Persistent infections can lead to chronic inflammation, causing cell damage, increased oxidative stress, and protein misfolding, which are key events observed in neurodegenerative pathology. Additionally, protein aggregates, such as amyloid-beta and tau in Alzheimer’s disease, and alpha-synuclein in Parkinson’s disease, can act as inflammatory triggers, exacerbating existing immune responses.

Moreover, infections can lead to the activation of various immune cells, such as the microglia, which become hyperactive and release proinflammatory cytokines and reactive oxygen species (ROS), causing oxidative damage to nearby neurons and glia.

Microglia and astrocytes can also release glutamate, contributing to excitotoxicity, a process by which nerve cells are damaged and killed through excessive activation of glutamate receptors.

Finally, chronic infections can suppress the immune system, leading to immunosenescence, a state of impaired immune function that is associated with aging.

In this state, the immune system will become less effective in clearing pathogens, leading to recurrent infections that can promote chronic inflammation and neurodegeneration.

Role of Infections in Specific Neurodegenerative Diseases

Alzheimer’s Disease

Alzheimer’s disease is characterized by a progressive loss of neurons, particularly in the hippocampus, which is associated with memory and cognition.

Studies have shown evidence of chronic neuroinflammation, increased oxidative stress and the presence of harmful protein aggregates, such as amyloid-beta and tau, which are considered hallmarks of Alzheimer’s disease.

There is a growing body of evidence that chronic infections, such as periodontitis, herpes simplex virus type 1, Chlamydia pneumoniae, and Borrelia burgdorferi, can contribute to Alzheimer’s disease pathology.

These infections can increase the production of amyloid-beta and enhance its deposition in the brain, leading to inflammation and neuronal loss. They can also exacerbate tau accumulation in the brain, leading to further neurodegeneration.

Parkinson’s Disease

Parkinson’s disease is characterized by the loss of dopamine-producing neurons in the substantia nigra, leading to tremors, stiffness, and difficulty with movement.

Studies have shown that oxidative stress, inflammation, mitochondrial dysfunction, and protein aggregation are potential factors contributing to the pathophysiology of Parkinson’s disease.

Several infections, including Campylobacter jejuni, Helicobacter pylori, and influenza A virus, have been associated with Parkinson’s disease.

Inflammatory responses triggered by these infections can cause damage to dopamine-producing neurons, exacerbate alpha-synuclein aggregation, and enhance neuroinflammation, resulting in further neurodegeneration.

Huntington’s Disease

Huntington’s disease is a genetic disorder that causes the progressive loss of neurons in the basal ganglia and cortex, leading to cognitive, psychiatric, and motor symptoms.

The disease is caused by the expansion of a CAG trinucleotide repeat in the huntingtin gene, leading to abnormal protein folding and aggregation.

Several studies have suggested that immune responses and inflammation have a role in the pathogenesis of Huntington’s disease. Inflammation can exacerbate oxidative stress and neuronal damage, leading to further neurodegeneration.

Additionally, infections such as viral encephalitis and other persistent infections can contribute to the progression of Huntington’s disease by enhancing inflammation and oxidative stress.

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons, leading to muscle atrophy, paralysis, and eventually death.

Although the causes of ALS are not yet fully understood, several factors have been proposed, including genetic mutations, protein aggregation, oxidative stress, and neuroinflammation.

Studies have shown that infections, such as enterovirus and the bacterium Porphyromonas gingivalis, may play a role in the onset and progression of ALS.

Viruses and bacteria can trigger immune responses and inflammation, leading to the production of damaging molecules, such as ROS, and promoting neuronal death. Additionally, chronic infections can lead to immunosenescence, further worsening neurodegeneration.

Preventing Infections to Reduce the Risk of Neurodegeneration

Preventive measures, such as vaccination, maintaining good hygiene practices, and treating infections promptly, may play a significant role in reducing the risk of neurodegeneration caused by infections.

Lifestyle changes such as a healthy diet, regular exercise, and adequate sleep can also boost the immune system’s effectiveness and reduce the risk of chronic inflammation.

Several studies have also suggested that anti-inflammatory drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), may decrease the risk of neurodegeneration associated with infections.

Other potential therapies include the use of antioxidant supplements, immunomodulatory drugs, and anti-inflammatory cytokines, which could help reduce oxidative stress, inflammation, and protein aggregation in the brain.

Conclusion

Neurodegenerative diseases are complex disorders, and their underlying causes are not yet fully understood.

However, there is mounting evidence that infections can contribute to the onset and progression of these diseases by promoting inflammation, oxidative stress, and protein aggregation. Preventive measures and treatments that target the immune system, inflammation, and oxidative stress may help reduce the risk of neurodegeneration caused by infections.