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LOS ANGELES — Air pollution is a growing concern for brain health, with mounting evidence linking it to cognitive decline and an increased risk of developing Alzheimer’s disease. However, researchers say a new type of drug could help shield our brains from some of pollution’s harmful effects.
Researchers at the University of Southern California (USC) have found that a medication called GSM-15606 can reduce the buildup of a toxic protein in the brains of mice exposed to air pollution. This protein, known as amyloid beta 42, has a strong connection to Alzheimer’s disease in humans.
The study, published in the journal Alzheimer’s & Dementia, focused on two common types of air pollution: nanoparticulate matter (nPM) from urban air and diesel exhaust particles (DEP). Both of these pollutants are small enough to be inhaled deeply into the lungs and potentially enter the bloodstream.
When mice breathed in these pollutants over eight weeks, their brains showed increased levels of amyloid beta 42. However, mice given GSM-15606 during the exposure period had significantly lower levels of this problematic protein.
GSM-15606 belongs to a class of drugs called gamma-secretase modulators. These medications work by tweaking an enzyme involved in producing amyloid beta, shifting its activity to create less of the harmful 42-amino acid form and more of a shorter, less troublesome version.
While GSM-15606 itself is no longer being developed for human use, similar drugs are in the pipeline. If proven safe and effective in humans, they could potentially be used to protect people living in highly polluted areas or those at higher risk of Alzheimer’s disease.
The study also revealed an intriguing and somewhat concerning finding: mice exposed to diesel exhaust particles showed a 25% increase in the size of fluid-filled spaces in their brains called ventricles. This enlargement could indicate some degree of brain shrinkage, though more research is necessary to understand its significance.
The findings add to a growing body of evidence linking air pollution to brain health issues. Previous studies have found that people living in areas with high levels of air pollution tend to show faster cognitive decline as they age and have a higher risk of developing dementia.
While the best solution would be to reduce air pollution levels globally, that’s a long-term challenge. In the meantime, approaches like the one explored in this study could help protect vulnerable populations from pollution’s harmful effects on the brain.
“Because gamma secretase is needed for normal functions body-wide, this drug was designed to modulate, but not inhibit, production of Aβ42,” says study senior author Caleb Finch, the holder of the ARCO/William F. Kieschnick Chair in the Neurobiology of Aging at the USC Leonard Davis School, in a university release. “This is the first example of a new drug developed to slow Alzheimer’s that may also protect aging individuals from the environmental risk factor of air pollution.”
Paper Summary
Methodology
The researchers exposed groups of mice to either filtered air, nanoparticulate matter, or diesel exhaust particles for 5 hours a day, 3 days a week, over 8 weeks. Some mice were also given food containing GSM-15606 throughout this period. After the exposure, the researchers examined the mice’s brains, measuring levels of various forms of amyloid beta and assessing the activity of enzymes involved in its production. They also used MRI scans to look at brain structure in some of the mice.
Key Results
Mice exposed to air pollution showed increased levels of amyloid beta 42 in their brains, but this increase was prevented in mice also given GSM-15606. The drug didn’t affect the activity of enzymes that produce amyloid beta, suggesting it works by changing how these enzymes function rather than how many are present. Mice exposed to diesel exhaust particles also showed enlarged ventricles in their brains.
Study Limitations
This study was conducted in mice, so the results may not directly translate to humans. The exposure levels and duration used in the study may not perfectly mimic real-world human exposure to air pollution. Additionally, while the drug reduced amyloid beta 42 levels, the study didn’t assess whether this led to improvements in cognitive function or behavior in the mice.
Discussion & Takeaways
The study suggests that gamma-secretase modulators like GSM-15606 could potentially help protect the brain from some of the harmful effects of air pollution. This is particularly relevant given the widespread exposure to air pollution worldwide and its increasingly recognized impact on brain health. The findings also provide further evidence for the link between air pollution and processes involved in Alzheimer’s disease, such as amyloid beta accumulation. The observation of enlarged ventricles in mice exposed to diesel exhaust particles is concerning and warrants further investigation.
Funding & Disclosures
The study was funded by grants from the Cure Alzheimer’s Fund and the National Institutes of Health. Two of the study authors, K.D. Rynearson and R.E. Tanzi, hold patents related to the GSM-15606 drug used in the study. These patents are assigned to the University of California-San Diego and Massachusetts General Hospital. The other authors declared no conflicts of interest.
