More than 50 years ago, U.S. Navy physicians stationed on the West Pacific island of Guam found a shocking number of people with a mysterious fatal brain disease.

The symptoms - gradual paralysis, sometimes with the tremors of Parkinson's and the dementia of Alzheimer's - looked like several diseases of old age. But this ailment struck people as young as 18.

Doctors eventually named the syndrome amyotrophic lateral sclerosis / parkinsonism-dementia complex (ALS-PDC). Locals call it lytico-bodig. Among the indigenous Chamorro, it was the leading cause of death on the island, killing a quarter of the adults in one village alone at its peak.

Ever since, researchers have been chasing the cause. And many have come to regard Guam as a sort of neurological Rosetta Stone, thinking it holds the key to understanding similar ailments everywhere.

"Solve Guam, and you have the road map to solve all other gene and environmental interactions leading to neurodegenerative disease," said John Q. Trojanowski, director of the Alzheimer's Disease Center at the University of Pennsylvania School of Medicine.

Now, a Hawaii-based research team thinks the answer lies in a favorite food of the Chamorros: the flying fox, a local bat with a four-foot wingspan, typically served up in coconut cream.

A slow poison that damages nerves may work its way up the food chain from palm-like cycad trees to the bats that eat cycad fruit. While devouring the flying foxes, the Chamorros may have unwittingly ingested the toxin, causing the unusual brain disease at a comparatively young age, according to the report in the Proceedings of the National Academy of Sciences.

Strangely, the same toxin has shown up in brain tissue samples of Canadians who died from Alzheimer's, 7,000 miles away.

Guam has an unusually large cycad forest, so researchers have suspected cycad seeds for a long time. But they've failed to prove the connection.

Although Chamorros eat cycad seeds themselves, they take pains to wash out the toxins before they grind the nuts into flour for tortillas. And studies have shown that humans would have to consume unrealistically huge quantities of cycad flour to build up high enough levels of the same toxin.

But flying foxes may deliver the fatal doses, according to ethnobotanist Paul Alan Cox, senior author of the paper.

In cycads, Cox and his colleagues found, the toxin may originate in bacteria living inside the tree roots. Measuring the toxin in the bacteria, the cycad seeds and the bats, scientists found a 100-fold jump in concentration at each successive level.

Cox and his colleagues also found the toxin, called BMAA, in brain tissue samples of six Chamorros who died from lytico-bodig as well as in the brain tissues of two people from Canada who had died from Alzheimer's, but not in the other 13 comparison samples from Canada.

"As a Canadian myself, it was a difficult day," said co-author Susan Murch, a plant biochemist from University of Guelph in Canada. "It gave the findings a bigger potential implication outside Guam, but our study was not designed to look at Alzheimer's in Canada. At this point, it's only an indication that the bacteria might exist in other ecosystems, and we need to look at what's going on there to understand what these findings mean."

Fortunately for the Chamorros, the disease rates have been steadily decreasing for 30 years, although spouses and children of people with ALS-PDC remain at slightly higher risk to develop the ailment than the general population.

The decline in the disease coincides with the disappearance of cycad-fed flying foxes, which the Chamorros ate to near-extinction after an infusion of guns and cash, starting in the early 20th century, made it easier to hunt and buy the animals.

Based on this correlation, Cox first proposed the bat theory two years ago, in a paper co-written with neurologist Oliver Sacks (author of the book upon which the movie Awakenings was based).

Other researchers are intrigued, but skeptical of the latest theory in the 50-year mystery, which the New Yorker magazine once called "one of the most isolated, sustained, complex, intensely studied epidemics of human neurodegenerative disease in history."

"Like any other plant, a cycad is a factory of chemicals," said neuroscientist Peter Spencer of the Oregon Health & Science University, who first targeted BMAA in cycads more than 10 years ago. Now Spencer thinks a more plentiful cycad neurotoxin, cycasin, may cause the brain disease by turning useful molecules in the body into toxic ones.

Meanwhile, neuroscientist Christopher Shaw and colleagues at University of British Columbia have discovered new toxins in cycad seeds.

Mice with a gene known to protect humans from Alzheimer's stayed healthier on a Guam cycad diet, while mice with a version of the gene that puts people at higher risk of Alzheimer's became sicker quicker on the same cycad chow.

For now, the mystery has no solution, just a fresh chapter ending with a new cliffhanger. "It's like an Agatha Christie novel," Cox said. "Here's the cast of characters: Who's the murderer?"

Copyright Carol Cruzan Morton