While brain scans are an essential part of testing for Alzheimer's disease, there is currently no single test that can diagnose the disease.
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WHEN LILIAN Calderón-Garcidueñas recruited children for a study probing the effects of air pollution, Ana was just seven years old.
The trim girl with an above-average IQ of 113 "was bright, very beautiful and clinically healthy," the physician and toxicologist recalls.
But now Ana (not her real name) is 11. And after putting her and 54 other children from a middle-class area of Mexico City through a new battery of medical and cognitive tests, Calderón-Garcidueñas found that something has been ravaging the youngsters' lungs, hearts - and, especially troubling - minds.
Brain scans and screening for chemical biomarkers in the blood pointed to inflammation affecting all parts of the brain, says Calderón-Garcidueñas, of the National Institute of Paediatrics in Mexico City and the University of Montana in the USA.
On MRI scans, white spots showed up in the prefrontal cortex. In the elderly, she says, such brain lesions tend to denote reduced blood flow and often show up in people who are developing dementia, including Alzheimer's disease.
In autopsies of seemingly healthy Mexico City children who had died in car accidents or other traumatic events, Calderón-Garcidueñas uncovered brain deposits of amyloid-beta and alpha-synuclein, proteins that serve as hallmarks of Alzheimer's and Parkinson's diseases.
Several years earlier, she had found similar abnormalities in homeless Mexico City dogs and exaggerated versions of the abnormalities in local 20- to 50-year-olds.
She has published studies linking the insidious changes to the metro region's air quality. The area's more than 20 million inhabitants make it one of the world's largest cities, a roughly 7,000 km2 region choking with smog and particles containing carbon, metals and more.
Most are nanoparticles - too small to see but just the right size to migrate into tissues throughout the body. Further clouding the air are solvents and other reactive gases - as well as toxins from livestock faeces.
Scientists already know that air pollution can impair airways and blood vessels. The emerging surprise is what it might do to the brain. Increasingly, studies have been highlighting inflammation-provoking nanopollutants as a potential source of nerve cell damage.
Calderón-Garcidueñas has been correlating Mexico City's stew of air pollutants with a suite of symptoms in people of all ages. In March 2010 in Salt Lake City at the annual meeting of the Society of Toxicology, Calderón-Garcidueñas unveiled some of her latest data. At age 11, Ana shows persistent, growing brain lesions, the toxicologist reported. As do the other Mexico City children surveyed.
They also exhibit cognitive impairments in memory, problem solving and judgment and deficiencies in their sense of smell compared with age-matched children from a cleaner city 120 km away.
Other toxicologists at the meeting presented data, largely from animal studies, tracking the movement of billionth-of-a-metre-scale particles into the brain, where they triggered inflammation and abnormalities characteristic of Alzheimer's or Parkinson's.
Until recently, most air pollution toxicology has focussed on impacts to the lungs and heart, observes James Antonini of the U.S. National Institute for Occupational Safety and Health's (NIOSH) lab in Morgantown, West Virginia.
The challenge now, he says, is to identify which pollutants are harming the nervous systems of Ana and others who live in areas with particularly dirty air.
