Creating a Simian Model of Guam ALS/PDC Which Reflects Chamorro Lifetime BMAA Exposures
The theory that β-N-methylamino-L-alanine (BMAA), a cyanobacterial toxin, contaminates traditional food supplies of the Chamorro people of Guam is supported by the recent finding that chronic dietary exposure to L-BMAA in vervets (Chlorocebus sabaeus) triggers the formation of neurofibrillary tangles (NFT) and β-amyloid plaques in the brain. In the first experiment, we found that all four vervets receiving a 210 mg/kg dose for 140 days developed NFT and sparse amyloid deposits. In the second experiment, all eight vervets receiving a 210 mg/kg dose for 140 days developed NFT and amyloid deposits, as well as all eight vervets that received only 21 mg/kg. Based on dietary surveys of the Chamorro people, we estimated lifetime chronic BMAA exposure at a high and a low level: 1) adult male Chamorros eating two flying foxes per month plus one 30 g serving of cycad flour per week; and 2) adult male Chamorros eating one 30 g serving of cycad flour per day combined with the consumption of eight flying foxes per month. The resultant cumulative lifetime Chamorro exposures ranged from 1 to 41 g/kg and are comparable to the total lifetime vervet exposures in our experiments of 2 and 22 g/kg, respectively. Furthermore, measured protein-bound BMAA concentrations of vervets fed L-BMAA powder are comparable to measured protein-bound BMAA concentrations in postmortem brain tissues of Chamorros who died with ALS/PDC.
KeywordsBMAA Neurofibrillary tangles β-Amyloid Guam ALS/PDC Nonhuman primate models Neurodegeneration Cyanobacteria
We thank Roberta Palmour and the late Frank R. Ervin, Amy Beierschmitt, and the staff of the Behavioural Science Foundation in St. Kitts for overseeing the care and dosing of the vervets, Dr. Peter Wyatt of Queen Mary University of London and Dr. Peter Nunn of University of Portsmouth for technical advice, Ms. Jane Cox and Mr. James Powell for dose preparation, Mr. W. Broc Glover for sample preparation, Dr. James Metcalf for useful discussions, Dr. Robert Switzer and his team at NeuroScience Associates in Tennessee for helpful discussions at the initiation of the study and choice of antibodies, Dr. Deborah Mash, Dr. David Davis and the staff of the Miami Brain Endowment Bank at the Miller School of Medicine for collection and management of the biospecimens reported in this study, and Ms. Marilyn Asay for helping to prepare the manuscript.
Compliance with Ethical Standards
This study was supported by the Josephine P. and John J. Louis Foundation, the William Stamps Farish Fund, Douglas and Elizabeth Kinney, and Patrick and Heather Henry.
This research was approved by the Institutional Animal Care and Use Committee (IACUC) of the Behavioural Sciences Foundation in St. Kitts. Animal care and health was monitored by an on-site DVM veterinarian.
Conflict of Interest
The Institute for Ethnomedicine has applied for a patent for screening potential drug candidates using BMAA-induced neurodegeneration (US 14/229,624).
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