Using a new, highly sensitive technique, British researchers have failed to find any trace of aluminum in the hard, star-shaped plaques that dot the brains of people with Alzheimer's disease.
And with their report, they have stirred up an old debate over whether aluminum is a cause, effect or completely inconsequential in the development of the degenerative brain disorder, which attacks memory, thinking and behavior.
For more than a decade, arguments have raged about the role of aluminum in the development of the disease. The metal has consistently been found in the brains of Alzheimer patients, and many scientists have suggested that it is a cause of the disease.
The theory is that susceptible people who are exposed to large amounts of aluminum in their water, food or even deodorants might go on to develop the disease, which afflicts as many as 4 million people in the United States.
Some scientists who questioned the aluminum hypothesis said it was more likely that the dead and dying brain cells acted like sponges, soakingup the metal.
But now Dr. Frank Watt and colleagues at Oxford University in England have suggested that the aluminum found in autopsies of Alzheimer brain tissue was actually a laboratory contaminant.
Aluminum is present in laboratory dust and in the stains that researchers use to prepare brain tissue for examination; that, the British scientists say, may have confounded results.
Dr. Watt and his colleagues used nuclear microscopy, a method that involves bombarding the tissue with protons and that does not involve staining it, and found no signs of aluminum in 105 plaques found in autopsies of brains of Alzheimer patients. They reported their results in the current issue of Nature, a British science journal.
Dr. Geoffrey Grime, a member of the Oxford group, said the researchers concluded that their finding "weakens the link between aluminum and Alzheimer's disease."
But the finding may not spell the end of the aluminum hypothesis. Instead, it shifts it to neurofibrillary tangles, the other abnormal structure found in the brains of Alzheimer patients. Many investigators have reported abundant amounts of aluminum in these tangles.
Dr. Daniel Perl of the Mount Sinai School of Medicine in New York said no one knew the relationship between plaques and tangles. And he added that it was perfectly reasonable to suspect that aluminum was linked to one of these pathological structures and not the other.
Dr. Grime agreed and said the Oxford group hoped to look at tangles with nuclear microscopy, which should help resolve the issue. "When we started this study, the interest was in plaques," he said.
The aluminum hypothesis had its origins in studies of epilepsy in rabbits. More than a decade ago, researchers observed that the animals would develop seizures when they were given doses of aluminum salts. On autopsy, the rabbits' brains were found to have tangles similar but not identical to those in the brains of Alzheimer patients.
Later, several groups of researchers found aluminum in tangles fromAlzheimer patients.
The amount of aluminum they found ranged from 10 to 100 parts per million, whereas normal brain cells have less than 2 parts per million, Dr. Perl said. Another study published a decade ago reported the discovery of aluminum in plaques.
With the publication of those reports, scores of investigators began to search for epidemiological evidence linking aluminum to the disease.
Some looked at people exposed to aluminum in their water supplies, while others investigated exposure to aluminum in antacids. But Dr. John Breitner, an Alzheimer researcher at Duke University, said the results of those studies were inconclusive.
Other investigators have studied whether drugs that remove aluminum from the brain could help patients retain their memories and ability to think. But Dr. Gene Cohen, acting director of the National Institute on Aging, said the results of those studies had also been inconsistent. Currently, he said, there are probably more researchers who have decided that the metal is innocuous than who consider it a threat.