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Science 31 July 1987:
Vol. 237. no. 4814, pp. 517 - 522
DOI: 10.1126/science.3603037
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Articles

Science, Vol 237, Issue 4814, 517-522
Copyright © 1987 by American Association for the Advancement of Science

articles

Guam amyotrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin

PS Spencer, PB Nunn, J Hugon, AC Ludolph, SM Ross, DN Roy, and RC Robertson

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 beta-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 corticomoto-neuronal 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.


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