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A recent study by researchers at the University of Southern California (USC) has demonstrated that an experimental drug could potentially protect against the detrimental effects of air pollution on the brain, specifically the development of Alzheimer’s disease.

The study, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, highlights a promising avenue for preventing Alzheimer’s in populations exposed to high levels of air pollution.

The research focuses on the relationship between air pollution and the formation of amyloid plaques, abnormal clumps of protein that are characteristic of Alzheimer’s disease. These plaques are found between nerve cells in the brain and are associated with cognitive decline.

Senior author Caleb Finch, a prominent researcher at USC, has extensively studied the effects of air pollution on the brain, particularly the impact of fine particulate matter emitted from vehicles, industrial sources, and other pollutants.

“Many studies have shown that poor air quality has a significant impact on the risk of Alzheimer’s and accelerates cognitive decline,” said Finch, who holds the ARCO/William F. Kieschnick Chair in the Neurobiology of Aging at the USC Leonard Davis School of Gerontology.

The study tested a drug called GSM-15606, a type of gamma-secretase modulator, which was developed by researchers at the University of California, San Diego (UCSD) and Harvard University. Gamma-secretase is an enzyme involved in the production of amyloid-beta, the protein that forms amyloid plaques. Unlike other drugs that inhibit gamma-secretase, GSM-15606 modulates the enzyme’s activity, potentially reducing amyloid-beta production without disrupting its essential functions in the body.

In the experiment, mice were exposed to air pollution, specifically ambient nanoparticulate matter and diesel exhaust particles, for eight weeks. During this period, one group of mice was fed GSM-15606. The results were significant: mice that received the drug had considerably lower levels of amyloid protein in their brains compared to those that were exposed to pollution but did not receive 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 explained. “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.”

The study was conducted by a team that included researchers from USC, Harvard, and UCSD. The work was supported by grants from the Cure Alzheimer’s Fund and the National Institutes of Health (NIH), highlighting the importance of collaborative efforts in addressing the growing public health challenge posed by Alzheimer’s disease.

The findings suggest that GSM-15606, or similar drugs, could one day be used as a preventive measure for those at risk of Alzheimer’s due to prolonged exposure to air pollution. Further research, including clinical trials in humans, is needed to determine the drug’s effectiveness and safety in people. The study represents a significant step forward in understanding how environmental factors like air pollution contribute to Alzheimer’s and offers hope for new preventive strategies.

Journal Reference:
Jose A. Godoy‐Lugo, Max A. Thorwald, Mafalda Cacciottolo, Carla D’Agostino, Ararat Chakhoyan, Constantinos Sioutas, Rudolph E. Tanzi, Kevin D. Rynearson, Caleb E. Finch, ‘Air pollution amyloidogenesis is attenuated by the gamma‐secretase modulator GSM‐15606’, Alzheimer’s & Dementia (2024). DOI: 10.1002/alz.14086

Article Source:
Press Release/Material by University of Southern California
Featured image credit: Gerd Altmann | Pixabay

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