How air pollution fuels Alzheimer’s and brain disease

Alzheimer’s disease is among the many health threats linked to air pollution – an ever-present and often invisible killer that claims up to seven million lives prematurely each year.

These lethal particles don’t just harm the lungs and heart; their effects extend far beyond, infiltrating the brain and contributing to neurological disorders.

A new study from Scripps Research has confirmed a strong correlation between air pollution and various brain diseases, including Alzheimer’s and autism.

Unmasking the effects of air pollution

The researchers unraveled the intricate link between brain cell activity and a chemical modification that might be triggered by a range of factors.

These factors include inflammation, aging, and environmental pollutants linked to air pollution, pesticides, processed food, and smoke from wildfires.

The experts found that this chemical modification, S-nitrosylation, interferes with normal brain cell function. In particular, it prevents brain cells from forming new connections, eventually causing cell death.

New hope for Alzheimer’s treatment

The research, published in February 2025, presents a breakthrough revelation.

Interfering with S-nitrosylation in a pivotal brain protein showed visible signs of reversing memory loss symptoms in Alzheimer’s mouse models and human-derived nerve cells.

“We’ve revealed the molecular details of how pollutants can contribute to memory loss and neurodegenerative disease. This could ultimately lead to new drugs that block these effects to better treat Alzheimer’s disease,” noted Stuart Lipton, the senior author of the study.

Lipton, who serves as a clinical neurologist and holds the Step Family Foundation Endowed Chair at Scripps Research, first discovered S-nitrosylation more than two decades ago.

He explained that this chemical process happens when a molecule bound to nitric oxide (NO) combines with sulfur atoms within proteins to create “SNO,” changing their functionality. This leads to what Lipton described as a “SNO-STORM” in the brain.

The buildup of NO occurs naturally in the body and is produced in response to inflammation or electrical stimulation.

However, NO can also be formed excessively due to small particulate materials and nitrate-related compounds that are found in or triggered by air pollution, wildfire smoke, pesticides, or processed meats.

The role of proteins in the brain

In their latest study, the researchers probed deeper into the impact of S-nitrosylation on a protein known as CRTC1.

This protein plays a significant role in controlling genes responsible for establishing and sustaining connections between brain cells – crucial for the learning process and long-term memory retention.

The research confirmed that excess NO leads to S-nitrosylation of CRTC1, which then prevents the protein from binding with another vital brain protein, CREB.

This disruption hinders the stimulation of other necessary genes for forming neuronal connections.

A new target to prevent Alzheimer’s

Following these discoveries, the team went a step further and genetically engineered a version of CRTC1 that was resistant to S-nitrosylation.

When introduced into human nerve cells derived from Alzheimer’s patient stem cells, this modified version demonstrated promising potential.

Signs of Alzheimer’s disease, including nerve cell connection deterioration and reduced nerve cell survival, were prevented.

In Alzheimer’s mouse models, this re-engineered version of CRTC1 revived the activation of genes vital for memory formation and synaptic plasticity – enhancing the brain’s ability to reinforce neuronal connections.

Reversing the impacts of air pollution

These findings offer crucial insights into how the toxins we breathe in from our environment, particularly vehicular pollution and wildfire smoke, accelerate brain aging and Alzheimer’s through S-nitrosylation.

“We could nearly completely rescue molecular pathways involved in making new memories. It suggests that this is a druggable target that could make a real difference in treating Alzheimer’s and potentially other neurological diseases,” said Lipton.

The study further highlights why Alzheimer’s risk heightens with age. As age progresses, the body’s antioxidant defenses weaken, leading to increased inflammation and higher NO levels; this makes proteins more susceptible to harmful S-nitrosylation reactions.

The research has unmasked the silent havoc that S-nitrosylation inflicts on countless proteins throughout our bodies.

“We’re learning that S-nitrosylation affects numerous proteins throughout the body, but reversing just some of these changes – like those on CRTC1 – could have a significant impact on memory function,” concluded Lipton.

The full study was published in the journal Proceedings of the National Academy of Sciences.

—–

Like what you read? Subscribe to our newsletter for engaging articles, exclusive content, and the latest updates. 

Check us out on EarthSnap, a free app brought to you by Eric Ralls and Earth.com.

—–