California’s Central Valley, famous for producing much of the food Americans eat, is also infamous for its inferior air quality and its high rates of poverty, housing insecurity and at-risk workers.
Increasing epidemiological evidence has shown a correlation between long-term exposure to fine particulate matter (PM2.5) and the incidence of Alzheimer's disease and related dementias (ADRD).
Areas with severe PM2.5 pollution — including the Central Valley — are often inhabited by low-income residents who are disproportionately affected by these environmental hazards.
A $2.2 million RO1 grant from the National Institutes of Health is funding a collaboration between UC Merced geosciences Professor Xuan Zhang and researchers at Johns Hopkins University and Georgia Institute of Technology. Over the next few years, the researchers aim to unravel the complex group of particulates that make up PM2.5 and study the specific pollutants associated with dementia and their underlying mechanisms.
“This is especially important for understanding the causes of ADRD and, importantly, environmental toxicant risk factors that are potentially modifiable,” Zhang said.
The Central Valley is a perfect place for this research. Heavy truck traffic on Interstate 5 and Highway 99 contributes significantly to PM2.5 emissions, as do wildfires, industrial operations in and around cities, agricultural practices such as burning agricultural waste, energy production, residential wood-burning stoves and fireplaces, and diesel emissions. The Valley's surrounding mountain ranges and sometimes-stagnant air also trap pollutants.
PM2.5, a significant component of air pollution, consists of tiny particles with a diameter of 2.5 micrometers or smaller – small enough to penetrate deep into the lungs and even enter the bloodstream.
Zhang explained that some PM2.5 originates from natural processes such as wildfires, but most of it stems from human sources such as vehicles, industry and agriculture.
The researchers plan to study whether and which pollutants could induce and speed cognitive decline. They aim to determine the impact of contaminants on a specific and common type of dementia called Lewy body dementia (LBD), which affects 1.4 million people and their families in the U.S.
LBD is a progressive disorder characterized by abnormal protein deposits called Lewy bodies in the brain. These deposits interfere with brain function, leading to cognitive, motor and behavioral symptoms, as well as mood disorders such as depression.
Lewy bodies are made up of a protein called alpha-synuclein (αS), and about 30% of Alzheimer’s disease patients with αS pathology generally display a more rapid rate of cognitive decline than subjects with Alzheimer’s alone.
Previous studies show that αS may enter through the nose or gut but spreads throughout the body to the brain.
“While epidemiological studies demonstrating an association of ADRD with pollutants is relatively abundant, there is a clear unmet need for more mechanistic research,” Zhang said. “This knowledge is critical to fully understanding the causes of LBD and translating that knowledge into novel prevention and treatment strategies.”
