More than 50 years ago, U.S. Navy physicians stationed on Guam found a shocking rate of amyotrophic lateral sclerosis, or ALS—about 50 to 100 times higher than expected. Now, a new paper in the Nov. 11 Proceedings of the National Academy of Sciences may revive one of the original ideas: that ingestion of plant neurotoxins causes, at least in part, the surprisingly common occurrence of neurodegenerative diseases, including parkinsonism/dementia complex (PDC), among the indigenous Chamorro people. The findings also hint that elsewhere, notably in Canada, dietary neurotoxins may play a role in neurodegenerative diseases such as Alzheimer's.
The new paper shows evidence that the neurotoxic non-protein amino acid BMAA (β-methylamino-L-alanine) may accumulate to dangerous levels as it travels through the food chain from cyanobacteria to flying foxes. The latter, crow-sized bats, are a prized food of the Chamorro, who boil them in coconut cream and eat them whole. Ethnobotanist Paul Alan Cox, director of the Institute for Ethnobotany at the National Tropical Botanical Garden in Kalaheo, Hawaii, and two coauthors report sharp increases in BMAA, starting with symbiotic cyanobacteria living in the specialized roots of cycad trees—palm-like plants that date back to the time of the dinosaurs.
In cultures of the cyanobacteria, once known as blue-green algae, the researchers found BMAA concentrations of about 0.3 micrograms per gram. When they examined the cycad seeds, one of the top 10 food sources for the flying foxes, they found about 37 micrograms per gram, although the outer skin of the seeds had a much higher concentration. In flying foxes, the mean BMAA concentration soared to 3,556 micrograms per gram, according to estimates based on samples from 50-year-old museum specimens.
In blinded assays of brain tissues from the frontal cortex of six Chamorros who died from ALS-PDC, PNAS coauthor Susan Murch, a plant biochemist from the University of Guelph in Canada, found a mean of 6 micrograms per gram of BMAA. Surprisingly, among the 15 control samples of brain tissue from Canada, two had similar levels of the non-protein amino acid. Later, identification confirmed that those two samples came from people who had died of Alzheimer's. The other 13 Canadian control brain tissues showed no measurable BMAA.
The incidence of ALS-PDC in Guam has dropped, shadowing reduced consumption of cycad-fed flying foxes by the Chamorro, who have eaten them nearly to extinction and now import other flying foxes for feasts of cultural significance, according to a paper in the June 2003 Conservation Biology by Cox and Sandra Anne Banack, associate professor of biology at California State University, Fullerton, also a coauthor on the latest paper. Originally, in the 1950s, a nutritionist had proposed that Chamorros ingest toxins from cycad nuts, which they ground into flour. In the 1980s, other researchers had demonstrated in monkeys the neurotoxicity of BMAA from cycad seeds. But follow-up experiments in mice suggested unrealistic amounts of cycad flour would need to be consumed to cause disease, especially since Chamorros take pains to wash out most of the toxins. Other researchers have looked at aluminum in the water and diet, as well as possible genetic components. A 1990 article in the New Yorker called it "one of the most isolated, sustained, complex, intensely studied epidemics of human neurodegenerative disease in history."
"We've shown that BMAA, a known neurotoxin, is produced by cyanobacteria and occurs in high levels in the brain tissues of people who died from neurodegenerative diseases in Guam, but we haven't proven it is the cause; for this you would need an animal model," said Cox, who is taking a 17-month sabbatical to look for potential BMAA "biomagnification" routes in the Kii peninsula of Japan, and in Papua New Guinea among the Auyu, who also have historically high rates of similar syndromes.—Carol Cruzan Morton