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Our major focus is the Parkinson-dementia complex (PDC) that afflicts Chamorros on Guam and surrounding Mariana Islands.  PDC is a unique neurodegenerative disease that remains a significant public health burden to the older members of this indigenous ethnic minority. Previously, PDC was often co-morbid with amyotrophic lateral sclerosis (ALS); however, the incidence of ALS among Chamorros has returned to levels comparable to the rest of the world over the last 50 years. Current data indicate that PDC is a complex phenotype that derives significant contributions from advancing age, inherited susceptibilities, and as yet to be clarified environmental factors that broadly ultimately derive from progressive ‘westernization’ of Chamorros or consumption of initiators or promoters that are indigenous to these islands.   No proposed environmental factor has withstood scrutiny as a sole cause of ALS or PDC, leading to speculation of a yet to be identified gene-environment interaction.


The cycad plant was an early target of suspicion as the source of an environmental toxicant that promoted or caused ALS/PDC, since it was noted that Chamorros had relied heavily on cycads for food and medicinal purposes. beta-Methylamino-L-alanine (BMAA), a nonproteinogenic amino acid, is synthesized by cyanobacteria, and cyanobacteria are found on the roots of cycads.  Indeed, cycad flour preparations contain BMAA.  BMAA can be toxic to neurons under some in vitro models.  In contrast, other groups have not been able to replicate BMAA-induced in vitro neurotoxicity,  and efforts to reproduce a neurodegenerative illness similar to ALS/PDC by feeding BMAA to non-human primates were not successful.  Finally, it seemed impossible for humans to ingest sufficient BMAA to achieve levels expected to produce neurodegeneration. 

Our results from tissue donated for research by individuals who died of PDC, and match controls, do not support the BMAA component of "cycad hypothesis".  For this reason are using sophisticated analytical techniques to discover environmental toxicants that might contribute to this enigmatic disease.