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.