8.02.2004

Dietary Impact on Alzheimer's Disease? Input from the South Pacific

Neurotoxins from blue-green algae present in certain foods or water can accumulate in proteins and might cause brain diseases like Alzheimer's after many years, suggests a new study.

The latest research explains how a devastating neurodegenerative disease common on the remote Pacific island of Guam can still strike people down decades after they have left the island.

The disease, called amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC), has symptoms resembling those of both Parkinson's and Alzheimer's disease. The brain damage it causes is similar to that found in Alzheimer's patients.

The latest theory is that the islanders' taste for flying foxes is to blame. A neurotoxin called BMAA found in the fruit of the cycads on which the flying foxes feed, is thought to become concentrated in the flying foxes' flesh. BMAA, in turn, is made by a blue-green alga, or cyanobacterium, that lives in the roots of the cycads.

But this theory does not explain everything. Many islanders who leave Guam develop ALS/PDC decades later. BMAA is a water-soluble chemical, which means the body should soon get rid of it. So how BMAA caused brain damage so long after exposure had puzzled scientists.

Now a team led by Paul Cox, director of the National Tropical Botanic Garden in Hawaii, has shown that that BMAA is sometimes incorporated into proteins in place of normal amino acids. BMAA's structure was already known to resemble that of the amino acids that make up the proteins in our body.

Levels of this protein-bound form of BMAA in the cycad flour eaten by islanders, in the flesh of flying foxes and in the brains of ALS/PDC victims, are typically around a hundred times higher than that of the free form, the team found.

Protein tangles

This BMAA would slowly be released as proteins are broken down, Cox suggests. So for years after eating contaminated food, people's brains would be exposed to low levels of the neurotoxin. What is more, the abnormal proteins containing BMAA could also damage the brain in several ways, for instance by binding together to form the protein tangles characteristic of both ALS/PDC and Alzheimer's.

The study also raises intriguing new questions. As controls, about 20 brain samples from Canada were also tested for BMAA alongside the eight samples from Guam. As expected, no BMAA was found in the brain of the 13 Canadians who had not died from neurological diseases. But protein-bound BMAA was found in the brains of eight Canadian victims of Alzheimer’s disease.

Cox stresses that the study does not prove that BMAA plays a role in Alzheimer's or other brain diseases. "The sample size that we have studied is too small," he says.

And it still has not been proven conclusively that BMAA is the cause of ALS/PDC on Guam, Cox adds. However, its presence in the brain could be a sign that people have been exposed to other, as-yet-unknown cyanobacterial toxins.

The idea is plausible, says cyanobacteria expert Hans Paerl of the University of North Carolina in Chapel Hill, US. Cyanobacteria are common in freshwaters and seas worldwide, and thrive in polluted, nutrient-rich waters. "Their influence is expanding as we nutrify the environment," he says.

For example, in China there is growing evidence that cyanobacterial contamination of drinking water is to blame for the high rates of liver cancer in some regions, says Paerl. "We are just starting to put the pieces of the puzzle together."

Proceedings of the National Academies of Sciences



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