Air Pollution and Alzheimer's Disease

Have you ever gone outside, taken a deep breath in, and abruptly discovered that the air was not exactly what you expected? Instead of spring flowers, the air smells like smoke and car exhaust, almost thick enough to taste. You may have found yourself wondering how breathing all of this in could possibly be good for you. And you’re right, it isn’t good for you.

The CDC reports that “transportation-related air pollutants are one of the largest contributors to unhealthy air quality,” and exposure to traffic-related air pollution (TRAP) has been shown to be responsible for a number of health problems, like cardiac and respiratory ailments, diminished lung function and even premature death. Now some new research from Emory University in Atlanta has linked exposure to traffic-related air pollution to Alzheimer’s Disease (AD).

The United States and much of Europe ranks at the relatively low end of this scale. A mean annual PM2.5 level of 12 micrograms per cubic meter was adopted by the EPA as an annual standard in 2016.

Wenhua Yu, MPH Tingting Ye, MSc Yiwen Zhang, MSc Rongbin Xu, PhD Yadong Lei, PhD Zhuying Chen, PhD Zhengyu Yang, MPH Yuxi Zhang, PhD Jiangning Song, PhD Xu Yue, PhD Shanshan Li, PhD Prof Yuming Guo, PhD, CC BY 4.0, via Wikimedia Commons

There are a number of pollutants emitted by vehicles on the road, among them benzene, formaldehyde, acetaldehyde, carbon monoxide and dioxide and particulate matter, both large and small. The study by Li et al., (2024) focused on this last component of air pollution, especially on very fine particulate matter called PM2.5. Particulate matter is labelled by the diameter of the particles in the air. PM2.5 is tiny, with a diameter of 2.5 microns or less, finer than a human hair, which measures a relatively hefty 50 to 70 microns across. The California Air Resources Board reports that car and truck emission are responsible for much of the PM2.5 found in polluted air. Because it is so small, PM2.5 particles are easily inhaled, making them prime causes of a number of health related problems.

In their study, Li et al., speculated that exposure to these tiny particulates might accelerate brain inflammation resulting in an acceleration of the neural pathologies associated with AD. The changes in the brain that mark AD as well as other forms of dementia are fairly well known. They include the accumulation of plaques and neurofibrillary tangles that are toxic to the neurons in the brain. Nedergaard (2013) put it succinctly saying “Essentially all neurodegenerative diseases are associated with mis-accumulation of cellular waste products…tau and βeta-amyloid [proteins] can accumulate as stable aggregates that are neurotoxic in conditions such as Alzheimer’s disease” (page 1529). Beta-Amyloid proteins form plaques, which are clumps of these proteins that accumulate outside of the neurons of the brain, blocking the messages normally being sent from one cell to another. Beta-Amyloid proteins interact with another kind of protein called tau proteins, that make up the skeletal structure of the neurons, causing them to clump together inside the cells forming what are called neurofibrillary tangles. These tangles ultimately cause the internal structure of the neuron to fall apart, resulting in cell death.

DNA methylation

Mariuswalter, CC BY-SA 4.0, via Wikimedia Commons

Li and colleagues also hypothesized that exposure to PM2.5would also trigger changes in DNA methylation (DNAm). In DNAm, a methyl group is added to cytosine, one of the four bases that make up DNA, which then regulates the process of gene expression or the way that gene instructions are carried out (Moore, Le and Fan, 2013). Li et al., examined how exposure to PM2.5 and DNAm affects the creation of plaques and tangles in the brain, one of the first studies to be carried out in humans.

Using postmortem brain tissue samples donated to the brain bank at the Emory Goizueta AD Research Center, researchers measured plaques and tangles in the prefrontal cortex. All of the samples came from donors who lived in the metropolitan Atlanta area who had been diagnosed with AD or probable AD before passing away in 1999. They also obtained records of the annual concentrations of traffic related PM2.5 in the 20-county area that makes up and surrounds car and traffic-heavy metro Atlanta, which they then used to estimate the donors’ exposure to PM2.5 at 1, 3 and 5 years prior to death.

They found that PM2.5 was significantly associated with DNAm in several genes that were known to be associated with inflammation in the brain, and so also associated with the plaques and tangles that characterize AD. They concluded that DNAm was a mediator between exposure to TRAP and the plaques and tangles that compromise brain function in AD. This study was the first to identify DNAm as the mediating step between exposure to pollution and the neuropathological changes seen in AD.

Li suggests that future research might look for changes in DNAm in tissue that is easier to access (i.e. doesn’t require waiting until after the death of the patient) to potentially serve as a biomarker for AD