Pollutant particles might make their way to the brain and damage it directly, or they might attack it from a distance, by triggering the release of inflammatory molecules.

Where the risk is greatest is far from clear. Burning just about anything produces PM2.5: oil and gas, firewood, vegetation. Federal- and state-funded networks of air quality monitors in the United States get turned off and on according to political whim, and are frustratingly uneven. According to the American Lung Association less than a third of U.S. counties have ozone or particle pollution monitors, and coverage is especially sparse in rural areas. Those that exist have only measured PM2.5 since 1997—before that, EPA did not monitor particles smaller than PM10.

Over the past several years, however, new computational models have made it possible to fill in some of the gaps in monitoring data, Gray says. In September 2016, NIEHS and the National Institute on Aging launched several new epidemiological studies that will use such modeling to look at the link between air pollution and brain health. One, based in Seattle, Washington, will estimate participants’ lifetime exposure to PM2.5 pollution and correlate it with the incidence of dementia, says Lianne Sheppard, a biostatistician at the University of Washington in Seattle.

For their study of the Seattle region, Sheppard and her colleagues will take advantage of a model they developed for an earlier study of air pollution and atherosclerosis. Creating it, she says, took “a huge amount of behind-the-scenes work.” First, they compiled more than a decade of air monitoring data on PM2.5 and other pollutants from 600,000 locations across the United States. For each location, they calculated 800 different geographic variables, such as the distance to ports, factories, refineries, residual oil, and roads. Then they fitted their models to the monitoring data using a 25-by-25-meter grid and estimated PM2.5 concentrations in each grid cell.

Building on the model, Sheppard and colleagues will create an even more detailed estimate of past air pollution levels in and around Seattle. To survey dementia in the region, the team will tap the Adult Changes in Thought study, which has monitored 5000 elderly people in the Seattle area for more than 20 years. Although all the participants were cognitively normal when they joined, at age 65 or so, roughly 1000 have since developed dementia, including 859 Alzheimer’s cases.

When the participants die and donate their brains to science, as more than 600 already have, pathologists examine their brain tissue for abnormal protein deposits, cerebrovascular damage, and other signs of cellular stress. Combined with genetic studies, Sheppard says, such analyses will allow her group to probe “not just the epidemiology of the relationship between air pollution and cognition, but start drilling down to mechanisms” that explain how airborne pollutants affect the human brain.

Some people may be more susceptible than others. In the Translational Psychiatry study, Chen’s team found that women carrying the Alzheimer’s risk gene APOE4 faced a disproportionately higher risk from pollution. And recently, Finch has started to examine the overlap—and potential synergy—between PM2.5 and cigarette smoke. The smoke is itself rich in ultrafine particles and can trigger the production of amyloid plaques and neuroinflammation in mouse models. Although smoking was once considered protective against Alzheimer’s, prospective studies have since established tobacco smoke as a major risk factor, he says. In 2014, for example, a report published by the World Health Organization attributed as much as 14% of Alzheimer’s disease worldwide to smoking.

Pollution may take a greater cognitive toll on the poor, in part because they are more likely to live in places with higher PM2.5 exposures, such as near major roadways or ports. Jennifer Ailshire, a USC sociologist, says stresses linked to poverty also could amplify the effects of the toxic particles. In one of her most recent studies, elderly people who rated their neighborhoods as stressful—citing signs of decay and disorder, such as litter and crime—did worse on cognitive tests than people who were exposed to similar pollution levels, but lived in less stressful neighborhoods, she says. “Living in L.A. [Los Angeles], we are all exposed to a lot of pollution, but some of us are fine,” she says. When seeking to reduce the negative health impacts from air pollution, cities “might want to try to focus specifically on reducing pollution in communities particularly vulnerable to these exposures,” she says.

But no one studying the suspected effects of pollutant particles on the brain is eager to do triage. If PM2.5 is guilty as charged, they say, the goal for policymakers worldwide should be to push down levels as far as possible. When all the research is in, Finch says, “I think [air pollution] will turn out to be just the same as tobacco—there’s no safe threshold.”

Source: http://www.sciencemag.org/news/2017/01/brain-pollution-evidence-builds-dirty-air-causes-alzheimer-s-dementia