Biophysical Characterization and Cross-Seeding Properties Of LFAOs, Novel Prion-Like Oligomers of the Amyloid-Beta Peptide Involved In Alzheimer’s Disease

Author

Morgan C. Woodrow, University of Southern Mississippi

Date of Award

Spring 5-2013

Degree Type

Honors College Thesis

Department

Chemistry and Biochemistry

First Advisor

Vijay Rangachari

Advisor Department

Chemistry and Biochemistry

Abstract

The amyloid-beta (Aβ) protein is known to play an important role in the etiology of Alzheimer’s disease (AD). Aβ peptide aggregates in the brains of AD patients to form soluble oligomers as well as insoluble fibrils. Oligomers of Aβ are now known to be the primary toxic agents in AD. Evidence is beginning to emerge regarding a conserved prion-like propagation mechanism in AD. One of the principal characteristics of prion diseases is their ability to self-propagate via a template-assisted-corruptive mechanism. Our lab has previously characterized a unique ‘Aβ prion’ called Large Fatty-Acid- Derived Oligomers (LFAOs). This project examines the ability of LFAOs to self- propagate and cross-seed the formation of aggregates among mutant varieties of the peptide. We observed the self-seeding and cross-seeding reactions of wild-type and Arctic (E22G) mutant varieties of LFAOs. Self-seeding of wild-type Aβ (1-42) (Aβ42) generated an increase in the amount of oligomer of the same size as the formed LFAOs, as did the cross-seeding of wild-type Aβ42 monomer with E22G LFAOs. Self-seeding of E22G monomer with E22G LFAOs, however, resulted in much larger aggregates. Cross- seeding of Aβ (1-40) (Aβ40) monomer with E22G LFAOs resulted in the formation of more oligomer of the same size as the seed. In addition, we have examined the stability of LFAOs in various experimental conditions.

Comments

Honors College Award: Top Thesis

Copyright

Copyright for this thesis is owned by the author. It may be freely accessed by all users. However, any reuse or reproduction not covered by the exceptions of the Fair Use or Educational Use clauses of U.S. Copyright Law or without permission of the copyright holder may be a violation of federal law. Contact the administrator if you have additional questions.

Recommended Citation

Woodrow, Morgan C., "Biophysical Characterization and Cross-Seeding Properties Of LFAOs, Novel Prion-Like Oligomers of the Amyloid-Beta Peptide Involved In Alzheimer’s Disease" (2013). Honors Theses. 122.
https://aquila.usm.edu/honors_theses/122