Scientists identify genetic clues linking air pollution to neurodegeneration

Scientists identify genetic clues linking air pollution to neurodegeneration

New research shows that toxic air can reshape gene activity in the brain, potentially setting the stage for Alzheimer's and Parkinson's and underscoring the need for early detection and stronger protection for at-risk workers.

Article published in a recent article in the JournalIscienceResearchers in Italy investigated how air pollution contributes to neurodegenerative disorders (NDs) through epigenetic modifications. She raised the potential of using epigenetic markers to detect early changes triggered by air pollution, particularly in high-risk groups. They emphasized the need for further research to guide occupational and preventive health strategies.

background

Young adults in polluted cities show alarming brain changes. Reduced histone markers (H3K9me2/ME3) and increased DNA damage signals were found in their brain tissue, reflecting Alzheimer's pathology decades before the typical age of diagnosis.

NDs are long-term conditions that involve the loss of nerve cells in the brain or nervous system, leading to significant problems with memory, thinking, mood, and physical function. Alzheimer's disease and Parkinson's disease are the most common and affect millions of people worldwide. As populations age, the number of people with these conditions increases. Many cases are associated with preventable risk factors, including poor lifestyle habits, low education or income, and exposure to environmental pollution.

Air pollution consists of harmful particles and gases from natural sources such as wildfires and human activities including fuel combustion, traffic and factory emissions. Particles can carry toxic substances including heavy metals, bacteria and volatile chemicals. Although air pollution is primarily linked to heart and lung disease, it is now also linked to brain damage and an increased risk of NDS. Certain workers, such as miners, factory workers and drivers, may be particularly at risk.

How air pollution affects the brain

Air pollution can affect brain health through two primary pathways: direct and indirect. The direct route involves ultrafine particles and certain gases entering the bloodstream or traveling through the nose to the brain, potentially causing damage to the blood-brain barrier (BBB) ​​and inflammation. Some pollutants such as nitrogen dioxide (NO₂) convert into active compounds that affect brain function, while others such as volatile organic compounds (VOCs) accumulate in brain tissue due to their fat-soluble nature. Although evidence of direct brain effects from these pollutants remains limited, studies have shown that substances such as nanoplastics, lead and manganese can cross the BBB and brain cells.

The indirect pathway involves pollutants that trigger inflammation or chemical signals (such as cytokines, extracellular vesicles, or lung/brain-derived exosomes) in organs such as the lungs or intestines. These molecules then travel through the bloodstream to the brain, disrupting its balance and potentially leading to cognitive and emotional problems. Air pollution can also disrupt gut and nasal microbes and affect brain health through gut brain or olfactory brain axes. While experimental evidence is still emerging, understanding these mechanisms may help identify early biomarkers of environmental brain damage, particularly in vulnerable populations such as workers in polluted environments.

Epigenetic pathways

Brain cells release distress signals into blood. Extracellular vesicles carrying epigenetic material from damaged neurons and astrocytes could become recognizable biomarkers of early potential, generating a “message in a bottle” from the brain.

Epigenetic changes regulate brain function without altering deoxyribonucleic acid (DNA) sequences. These changes are crucial for brain development, synaptic plasticity and memory, but are also sensitive to environmental stresses such as air pollution. Chronic exposure to pollutants can disrupt these epigenetic processes, potentially leading to NDs. There is evidence that such exposure can increase the expression of harmful genes, reduce the activity of protective genes and alter non-coding ribonucleic acids (RNAs). These changes can occur long before symptoms, highlighting epigenetics as both a risk factor and an early biomarker for NDs.

Pollutants in the air can disrupt brain function by altering non-coding RNAs and DNA methylation, both of which regulate gene expression. Animal and human studies show that these changes are associated with memory loss, inflammation, and NDs. However, most human findings come from peripheral blood samples, not brain tissue, which limits clinical interpretation. Toxins such as toluene, manganese and lead can reduce the activity of protective genes or increase the production of harmful proteins in the brain. Some effects can even be passed down to descendants. Air pollution also alters DNA methylation in blood and brain tissue, potentially increasing the risk of disease across the lifespan, particularly with early or long-term exposure.

Few studies have examined how air pollution affects histone modifications in neurodegenerative diseases (NDs) due to technical challenges. However, early results show links between air pollution and altered histone markers, DNA damage and Alzheimer's disease pathology in both humans and mice. Prenatal exposure to particles influences brain development, particularly in males, due to histone demethylation, highlighting sex-specific vulnerabilities. Plastic particles and heavy metals also disrupt histone modifications and cause oxidative stress, memory loss and neuroinflammation. In particular, some experimental evidence for histone modifications (e.g., manganese-induced changes) comes from injection studies rather than inhalation exposure, creating uncertainties about real inhalation risks. Histone deacetylase inhibitors and compounds such as butyrate (studied in lead-exposed mice) show potential in reversing some of these effects and provide avenues for future ND treatments.

Conclusions

Workers who handle plastics face invisible threats. Nanoparticles from manufacturers or damaged breathing devices enter the brain, causing temporary olfactory damage and inflammation – early warning signs of neurodegenerative diseases.

Recent research shows strong links between air pollution and NDS mainly through epigenetic changes. Pollutants can alter DNA methylation, non-coding RNA expression, and histone modifications, all of which contribute to brain inflammation and damage. New methods such as analysis of extracellular vesicles in the blood can help detect these changes without invasive procedures. However, studying histone modifications remains technically challenging. Key gaps remain. Real-world air pollution is complex, making it difficult to study precise effects. Factors such as particle size, individual health and early life exposure influence risk but are not fully understood. Anatomical differences between animal models and humans (e.g., nasal structure) further complicate the translation of inhalation studies. Most research focuses on older adults, short-term exposure, and a limited number of pollutants, overlooking long-term and early effects. Diseases such as multiple sclerosis, amyotrophic lateral sclerosis (ALS) and Huntington's disease are also being studied.

Future studies should be long-term, include younger populations, and consider less studied contaminants and routes of exposure such as diet or gut-brain interactions. The combination of omics technologies and artificial intelligence could help identify biomarkers and lead to the development of preventative therapies. Improved occupational and environmental protection, particularly for high-risk groups, are also essential to reduce the risk of ND. Addressing regulatory implications requires validation of epigenetic tools for clinical use.

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