Guam Amyotrophic Lateral Sclerosis--Parkinsonism--Dementia Linked to a Plant Excitant Neurotoxin

• Published in: Science (American Association for the Advancement of Science) Vol. 237; no. 4814; pp. 517 - 522
• Main Authors: Spencer, Peter S., Nunn, Peter B., Hugon, Jacques, Ludolph, Albert C., Ross, Stephen M., Roy, Dwijendra N., Robertson, Richard C.
• Format: Journal Article
• Language: English
• Published: Washington, DC The American Association for the Advancement of Science 31-07-1987; American Association for the Advancement of Science
• Subjects: Alanine; Alzheimer's disease; Alzheimers disease; Amino Acids, Diamino - toxicity; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - chemically induced; Animals; Basal Ganglia Diseases - chemically induced; Biological and medical sciences; Causes of; Cycadales; Cycas circinalis; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia; Environment; Environmental Exposure; Guam; Health aspects; Macaca fascicularis; Male; Medical research; Medical sciences; Motor cortex; Motor Cortex - drug effects; Motor neuron disease; Motor Neurons - drug effects; Nervous system; Nervous system diseases; Neural Conduction - drug effects; Neurology; Neuromuscular Diseases - chemically induced; Neurons; Neurotoxic agents; Neurotoxins - toxicity; Parkinson disease; Plants, Toxic; Primates; Spinal cord; Spinal Cord - drug effects; Substantia Nigra - drug effects; Guam; Human; Plant; Nervous system diseases; Guam Island; Neurotoxin; Parkinson disease; Amyotrophic lateral sclerosis; Degenerative disease; Dementia
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.3603037

The decline in the high incidence of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer-type dementia among the Chamorro population of the western Pacific islands of Guam and Rota, coupled with the absence of demonstrable viral and hereditable factors in this disease, suggests the gradual disappearance of an environmental factor selectively associated with this culture. One candidate is seed of the neurotoxic plant Cycas circinalis L., a traditional source of food and medicine which has been used less with the Americanization of the Chamorro people after World War II. Macaques were fed the Cycas amino acid β -N-methylamino-L-alanine, a low-potency convulsant that has excitotoxic activity in mouse brain, which is attenuated by N-methyl-D-aspartate receptor antagonists. These animals developed corticomotoneuronal dysfunction, parkinsonian features, and behavioral anomalies, with chromatolytic and degenerative changes of motor neurons in cerebral cortex and spinal cord. In concert with existing epidemiological and animal data, these findings support the hypothesis that cycad exposure plays an important role in the etiology of the Guam disease.