Scientists in 2004 studied the brain tissue of children and young adults in Mexico who had died of accidents and were stunned by what they found -- a discovery that rocked the world of neuroscience and has gone largely untested until now.
Almost all of the young people had evidence of Alzheimer's protein plaques scattered throughout their brain tissue.
The only factor linking one case to another was air pollution in Mexico City, which led scientists at the time to hypothesize that smog might be a trigger of Alzheimer's disease -- and that the mind-robbing damage might start early in life.
Now a new group of scientists has picked up where the first team left off. So far, it appears a link may exist between inhaling pollutants and developing damage in the brain.
A nationwide study last year followed the fate of nearly 20,000 women over a 10-year period and found that inhaling pollutants, such as those found in any metropolitan area, exacerbated problems with attention span and escalated memory loss.
Another investigation reported last year, which focused on Boston, revealed that on days when concentrations of traffic-related pollutants were up, the number of strokes increased.
Dr. Heather Volk of the University of Southern California reported last fall that exposure to traffic-related pollution during pregnancy and a child's first year of life appear to be associated with an elevated risk of autism.
The key pollutants, she found, were vehicle-related particulate matter and nitrogen dioxide, a leading precursor of ozone, also known as smog.
In Manhattan, Dr. Sam Gandy, director of the Center for Cognitive Health at The Mount Sinai Hospital, has begun a series of studies testing whether air pollution can trigger the pathological changes linked to Alzheimer's.
His research, which was inspired by the findings in Mexico, focuses on laboratory animals.
Gandy said few studies have examined air pollutants as a possible cause. And while the epidemiologic study of Mexican children and young adults suggested the possibility, that evidence was circumstantial. "You rarely see this kind of pathology before the age of 40 and never, ever in children," Gandy said.
The 2004 autopsy research raised key questions for Gandy, primarily when and how Alzheimer's begins in the brain and which pollutants in contaminated air are so capable of unraveling the mind.
In the original study in Mexico, Dr. Lilian Calderón-Garcidueñas of the University of Montana examined 43 brains from children and young adults, the oldest of whom was 40. Half of the specimens were from children younger than 17.
Of those studied, 35 were lifelong residents of Mexico City while the eight control subjects, people who lived outside the air pollution of Mexico City, were from the rural areas of Tlaxcala and Veracruz.
Calderón-Garcidueñas and her team looked for changes in genes and immune-system markers. They also searched for physical evidence indicative of Alzheimer's disease and found it in residents of Mexico City -- but not in the tissue of people of the same age from unpolluted rural areas.
In the lab, Gandy and colleagues exposed mice to the common gases and nanoparticles of air pollution for three hours. When the mice were autopsied, they showed a 72 percent to 129 percent increase in the levels of beta amyloid, a key protein associated with Alzheimer's. "We were startled when three hours of air pollution exposure for the mice showed such a rapid and dramatic elevation," Gandy said.
Dr. Jeremy Koppel, a research scientist at the Litwin-Zucker Research Center for the Study Alzheimer's disease and Memory Disorders in Manhasset, called the findings exciting. "What is interesting about this study is that it followed the epidemiological research," said Koppel, referring to the order of studies. Koppel was not involved in either investigation.
"Epidemiology on its own doesn't tell us the whole story," Koppel said. "But when you combine the epidemiology with a thoughtful experiment like this, it lends credibility to the notion that air pollution may exacerbate amyloid pathology," he said of the protein linked to Alzheimer's.
What's still missing, added Koppel, is whether pollution somehow influences "tau," another aberrant protein linked to Alzheimer's disease.
Gandy said he hopes to further test his hypothesis. "The air we breathe affects our entire bodies," said Gandy, so it is not far-fetched to explore an effect on the brain.