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A Mechanistic Understanding Of Self-Propagating Amyloid-Β Oligomer Conformations In Alzheimer Disease, Dexter Nathanael Dean

Dissertations

Alzheimer disease (AD) is a fatal neurodegenerative disorder characterized by the widespread deposition of proteinaceous plaques abundant in amyloid-β (Aβ) aggregates. Although the plaques mainly contain high molecular weight, insoluble Aβ fibrils, the low molecular weight soluble aggregates called oligomers have been shown as the primary toxic species responsible for synaptic dysfunction and neuronal loss in AD. The process of aggregation is nucleation-dependent, but also highly stochastic and inhomogeneous resulting in biophysically diverse assemblies. Recent advances in the field indicate a potential correlation between the phenotypic diversity observed in AD subtypes and aggregate polymorphism. Therefore, understanding the molecular mechanisms which …