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dc.contributorScholtz, John M.
dc.creatorRidinger, Katherine V.
dc.date.accessioned2011-02-22T22:23:44Z
dc.date.accessioned2011-02-22T23:45:27Z
dc.date.accessioned2017-04-07T19:57:51Z
dc.date.available2011-02-22T22:23:44Z
dc.date.available2011-02-22T23:45:27Z
dc.date.available2017-04-07T19:57:51Z
dc.date.created2009-12
dc.date.issued2011-02-22
dc.identifier.urihttp://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7339
dc.description.abstractAmyloid fibrils results from a type of ordered polypeptide aggregation that is associated with ailments such as Alzheimer's disease (AD). Annually, millions of people in the United States alone develop and die from AD. Therefore, it is necessary to understand not only the process of amyloid formation, but also the causes of this specific type of aggregation. This study used ABeta(25-35) since it is a fragment of the Alzheimer?s peptide that behaves like the full length peptide found in patients with AD. To study the process of amyloid formation, several methods were used so that a more complete picture of the stepped aggregation process could be realized. Several oligomeric species were detected and described many of which could not have been observed without using the complete battery of methods utilized here. The oligomeric species detected included a novel 'rolled sheet' that appeared to be the immediate precursor of amyloid fibrils, and two supermolecular species that appear after amyloid fibrils were formed. In determining the causes of amyloid formation, two significant discoveries were made. First, by partial sequence randomization, truncation, and Ala scanning mutagenesis, the critical amyloidogenic region of ABeta(25-35) was found to be residues 30-35. This critical core region is important because it is thought to be the region that initiates amyloid formation, therefore knowing the residues involved in the region is a useful tool for developing methods of fibril formation prevention. Second, by inserting all naturally occurring amino acids into position 34 of ABeta(25-35), three distinct classes of variants were observed and the effect of several physiochemical properties on amyloidosis were examined. Hydrophobicity, solubility, and ?-strand propensity were found to affect aggregation to the greatest extent. Also within these two studies, our results suggest that early oligomers are the cytotoxic species as opposed to amyloid fibrils or other larger macromolecular assemblies.
dc.language.isoen_US
dc.subjectphysiochemical properties
dc.subjectThioflavin T fluorescence
dc.subjectdymanic light scattering
dc.subjectelectron microscopy
dc.subjectcytotoxicity
dc.titleA Study of the Process and Causes of Abeta(25-35) Amyloid Formation
dc.typeBook
dc.typeThesis


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