USC researchers demonstrate how a novel compound reduces Alzheimer’s-associated proteins in mice exposed to air pollution
A groundbreaking study from the University of Southern California (USC) Leonard Davis School of Gerontology has revealed a potential new avenue for protecting the brain against air pollution’s harmful effects on Alzheimer’s disease risk. The research, published in Alzheimer’s & Dementia, shows that a drug called GSM-15606 can significantly reduce levels of a protein associated with Alzheimer’s in mice exposed to air pollution.
Air Pollution and Alzheimer’s: Unraveling the Connection
Air pollution has long been linked to an increased risk of Alzheimer’s disease and accelerated cognitive decline. Fine particulate matter from sources like car exhaust and factory emissions can trigger systemic inflammation and promote the formation of amyloid plaques in the brain – a hallmark of Alzheimer’s disease.
These plaques consist of aggregated peptides called Aβ42, which clump together between nerve cells. As air pollution levels rise, so does the risk of developing these harmful protein accumulations.
Caleb Finch, senior author of the study and USC University Professor, explains: “Many studies have shown that air quality has a sizeable impact on risk of Alzheimer’s and accelerates cognitive decline.”
A Novel Approach: Gamma-Secretase Modulators
The USC team’s research focused on a class of drugs called gamma-secretase modulators (GSMs). Specifically, they tested GSM-15606, developed by study co-authors Rudolph E. Tanzi of Harvard and Kevin D. Rynearson of the University of California, San Diego.
Over an eight-week period, mice were fed GSM-15606 while being regularly exposed to air pollution in the form of either ambient nanoparticulate matter (nPM) or diesel exhaust particles (DEP). The results were striking: mice given the drug showed significantly lower levels of Aβ42 in their brains compared to those exposed to pollution without the drug.
“Because gamma secretase is needed for normal functions body-wide, this drug was designed to modulate, but not inhibit, production of Aβ42,” Finch said. “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.”
Why it matters: With air pollution affecting millions of people worldwide and Alzheimer’s disease rates on the rise, this research offers hope for a potential preventive measure. If further studies confirm these findings in humans, GSM-15606 could become a valuable tool in reducing Alzheimer’s risk for those living in areas with high air pollution levels.
The study’s implications extend beyond individual health, highlighting the urgent need for better air quality regulations and cleaner energy solutions to protect public health on a broader scale.
It’s important to note that while these results are promising, the research is still in its early stages. The study was conducted on mice, and further research is needed to determine if similar effects would be seen in humans. Additionally, questions remain about potential side effects of long-term use of gamma-secretase modulators and their efficacy in different populations.
Looking ahead, the USC team and other researchers in the field will likely focus on several key areas:
1. Human trials to assess the safety and efficacy of GSM-15606 in people exposed to high levels of air pollution.
2. Investigation of the drug’s potential benefits for other neurodegenerative diseases linked to air pollution exposure.
3. Exploration of combination therapies that could enhance the protective effects of GSM-15606.
4. Development of more targeted delivery methods to maximize the drug’s impact on the brain while minimizing potential systemic effects.
As our understanding of the complex relationship between environmental factors and brain health continues to grow, research like this paves the way for innovative approaches to preventing and treating Alzheimer’s disease. It also underscores the critical importance of addressing air pollution as a public health issue with far-reaching consequences for cognitive health and aging populations worldwide.
