Cycad Toxins and Neurological Diseases in Guam: Defining Theoretical and Experimental Standards for Correlating Human Disease with Environmental Toxins

Abstract

<jats:p>Consumption of <jats:italic>Cycas micronesica</jats:italic> seed tissue has been associated with the amyotrophic lateral sclerosis–parkinsonism dementia complex (ALS–PDC) of the Western Pacific. However, failures to document vital plant and neighborhood descriptors and pronounced variability in toxin concentrations noted within and among studies obfuscate decades of research on this subject. We discuss the theoretical and experimental constraints of plant tissue sampling in relation to human disease research. Comparisons are made between this approach and methods used throughout the history of ALS–PDC research, most notably very recent reports concerning β-methyl-amino-alanine. Methods for studying possible plant neurotoxins need to be standardized and must follow rigorous criteria to be valid in principle. Our discussions reveal why these criteria are essential and highlight the impact that natural variations have on environmental toxin quantification and interpretation. Past research on cycad toxins is deficient on experimental and theoretical grounds, and interpretation of published data is dominated by ambiguities. This area of study as conventionally conceived and carried out needs transforming. We argue that future empirical studies should honor appropriate plant science standards concomitantly with medical science standards. This dual focus will ensure appropriate sampling scheme, sample size, and reporting of background plant and community factors known to influence phenotypic plasticity.</jats:p>

Neurodegenerative Diseases: Neurotoxins as Sufficient Etiologic Agents?

“…The largest fraction of sterol glucosides in cycad is usually b-sitosterol b-D glucoside (BSSG), however the absolute amounts and ratios of the different sterol glucosides can vary considerably between batches of cycad seeds. These variations likely arise due to differences in the season harvested, locale, and, most crucially, seed age (Marler et al 2005a): Cycad sterol glucoside concentrations, especially in young seeds, appear to be considerably higher than for most other plants studied to date (Marler et al 2005b).…”

Magnetic Resonance Microscopy and Immunohistochemistry of the CNS of the Mutant SOD Murine Model of ALS Reveals Widespread Neural Deficits

“…Guamanian ALS-PDC is associated with consumption of putative exogenous neurotoxins found in flour made from the seed of a local taxa of cycad (Cycas micronesica K.D. Hill, previously erroneously classified as C. circinalis) (Marler et al 2005).…”

Phenotypic Characteristics as Predictors of Phytosterols in Mature Cycas micronesica Seeds

“…fruit set, and Spayd et al (1986) reported a decrease in fruit acid, anthocyanin, and sugar concentrations with increased sweet cherry ( Prunus avium L.) fruit set. These reports led us to previously predict (Marler et al, 2005a) that the natural variation in seed number per reproductive event would be correlated with the range in seed chemistry in cycad plants. We have now determined that C. micronesica seed gametophyte sterol and steryl glucoside concentrations are not correlated with seed set within a robust range of one to 76 seeds per plant.…”

“…Seed maturation requires 20 to 24 months, but viable seeds can be harvested from plants as early as 12 months with postharvest embryo development. All cycads are characterized by an abundance of secondary compounds (Marler et al, 2005a). Some cycad compounds are toxins, and the study of these toxins may improve our understanding of health issues in relation to the myriad plant secondary compounds to which humans are exposed (Shaw et al, 2007).…”