Researchers find clue to unraveling mystery of Guam brain disease
Stars and Stripes March 20, 2023
Researchers have found that high concentrations of abnormally formed proteins in the brain are at the root of a mysterious neurodegenerative disease that has plagued Guam natives for more than a century.
The disease, called ALS/parkinsonism-dementia complex but long known on Guam as lytico-bodig, primarily afflicts the native Chamorro people living on the Pacific island.
Symptoms include tremors, arm and leg paralysis, lost memory and spells of dementia. The condition worsens over time and in most cases leads to death.
The study’s findings could help to further understand other neurological conditions, such as Alzheimer’s disease, Parkinson’s disease and ALS, also known as Lou Gehrig’s disease, according to a news release from the Uniformed Services University in Maryland, whose researchers collaborated in the study.
While the etiological cause of lytico-bodig remains unclear, the study published Monday in the Proceedings of the National Academy of Sciences is the first to find that the disease involves the accumulation of “prions,” proteins that form with abnormal folds and can spread in the brain and corrupt its function, the release said.
Researchers used newly developed tests to examine preserved brain tissue from Chamorro people who died with the disease. The highly sensitive tests revealed high concentrations of two types of proteins, tau and beta-amyloid, that had morphed into prions, the release said.
The term prion, short for proteinaceous infectious particle, was coined by Stanley Prusiner, who was awarded the Nobel Prize in Physiology or Medicine in 1997 for his groundbreaking findings on the link between prions and brain diseases.
Prusiner, now at the University of California-San Francisco, was lead author of the new study.
Among prion-related diseases in humans are Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease and kuru.
Perhaps the best known example among animals is “mad cow disease,” or bovine spongiform encephalopathy, a chronic wasting disease that is now found mainly in deer and elk.
Lytico-bodig, however, is unlike any other neurodegenerative disease and found only in Guam.
Although the disease was quite likely afflicting the people of Guam in earlier times, the first official reports of it were made in 1904, according to a 2017 article in Penn Medicine Magazine.
Serious study of the malady only began after American forces retook the U.S. territory from the Japanese during World War II.
“By the mid-1950s, it was a full-blown epidemic on an island of 60,000, afflicting people at a rate 100 times greater than similar neurodegenerative diseases did in other parts of the world,” the Penn Medicine Magazine article states.
At the epidemic’s height, more than 10% of adult deaths on the island were attributable to the disease, according to the Uniformed Services University news release.
Over the years, scientists have hypothesized about the cause of the disease, looking at everything from genetics, cycad trees, algae, parasites, bats and metallic compounds found in the soil. None has been conclusive.
A genetic cause has been largely ruled out because the disease was found in non-Chamorro people who lived long-term on the island.
In addition, if the gene for the disease were passed on to each new generation, the incidence of the disease would remain relatively constant. But cases of the condition waned in the decades after the 1950s, and today it has virtually disappeared, according to the new study.
“We’re excited about these findings, which, although they do not explain the underlying cause of the disorder, they do provide answers for how the disease spreads through the brain and produces its devastating effects on brain function,” Dan Perl, a professor of Neuropathology at Uniformed Services University and study co-author, said in the release.
“The findings reported here could have a significant impact on both civilian and military health care through further research and ultimately provide answers to why this disease has been endemic to Guam,” he said.