George Cutsail III, Chemistry
Copper Amyloid-beta Complex in Alzheimer’s Disease
Faculty Mentor: Dr. Veronika A. Szalai
Alzheimer’s disease (AD) is the seventh leading cause of death in the United States. Extracellular proteinacous plaques of the amyloid-beta (Aβ) peptide are linked to dementia in patients. Metal ions like copper (Cu) are in the Ab plaques from AD patients, but the significance of this finding with regard to disease etiology is unknown. We aim to characterize the interaction of copper with Aβ to elucidate its role in AD. The Aβ gene has been amplified by PCR and ligated into a modified pET-21 vector designed by Dr. Garvie (UMBC, Chemistry and Biochemistry). This vector allows for controlled expression and includes a protease site that allows for cleavage of the Aβ peptide. Expression will be evaluated using gel electrophoresis. The Cu:Ab complex changes its size/structure over time and the effect of these changes on neurotoxicity is not known. We will determine neurotoxicity of these Cu:Ab complexes using a rapid neurotoxicity assay developed by Dr. Good (UMBC, Biochemical Engineering). After we have identified which Cu:Ab complex has the largest effect on neuron survival, we will determine its structure using site directed spin labeling. Correlation of neurotoxicity with Cu:Ab structure will aid drug intervention strategies for AD.