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Development and application of gas chromatography assays for detection of environmental toxins and cerebrospinal fluid biomarkers

Posted on:2011-08-16Degree:Ph.DType:Thesis
University:University of WashingtonCandidate:Snyder, Laura RoseFull Text:PDF
GTID:2444390002464976Subject:Health Sciences
Abstract/Summary:
The high incidence rate of amyotrophic lateral sclerosis (ALS) and Parkinson dementia complex (PDC) on Guam following World War II sparked great interest in identifying possible causes. Studies showing that there is no apparent viral cause or genetic pattern of disease resulted in an intense search for environmental contributors to this phenomenon. An unusual amino acid found in cycads, beta-methylaminoalanine (BMAA), has been the focus of numerous investigations and even after 50 years, its relevance in the development of PDC and Guam ALS is still questionable. Recent studies implicating BMAA as a trigger for neurodegeneration have re-ignited the "cycad hypothesis," although there is controversy surrounding this claim. BMAA reportedly accumulates in brain tissue, and this finding has been published in several journals. Two chapters of this work describe new and sensitive methods to test the theory of BMAA bioaccumulation.;In addition to probing human tissue for neurotoxins, this work also describes the current problem of metabolomics studies in human samples. Recent advances in comprehensive gas chromatography provide an interesting approach to more thoroughly study the human cerebral spinal fluid metabolome. An unbiased chemometric analysis has been applied to detect specific markers of neurodegeneration. To address the inherent problem of biological variation, longitudinal samples have been used for an in-progress study that looks at the effects of diet on cognitive function.
Keywords/Search Tags:BMAA
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