(631e) Tannic Acid Inhibits Amyloid Beta Aggregation with Specificity for an Oligomer Species Conference: AIChE Annual MeetingYear: 2014Proceeding: 2014 AIChE Annual MeetingGroup: Food, Pharmaceutical & Bioengineering DivisionSession: Fundamentals of Protein Folding in Diseases Time: Thursday, November 20, 2014 - 9:48am-10:06am Authors: van der Munnik, N., University of South Carolina Moss, M. A., University of South Carolina Alzheimer’s disease (AD) is a debilitating disease that is the sixth leading cause of death in the United States. It is the only disease that is in the top ten most lethal that currently has no known cure. One of the hallmarks of AD is the presence of amyloid β (Aβ) aggregates in the brains of those afflicted. Aβ is a small protein, usually 40 or 42 amino acids long, with no known function or native conformation. This protein aggregates through diverse mechanisms to progress from monomers to soluble oligomers and ultimately the insoluble fibrils that deposit in the brain. A significant body of evidence now suggests that the most toxic species of Aβ aggregates are soluble oligomers. These findings coupled with the current understanding of the etiology of AD point to general disruption of the aggregation pathway and, more specifically, inhibition of the formation of the toxic oligomers of Aβ as promising strategies for a potential cure. Tannic acid (TA), a polyphenol present in many plants, has been found to have remarkable effects on the aggregation of Aβ. TA has been shown to inhibit aggregation of Aβ, destabilize preformed aggregates, and remodel Aβ oligomers. Accordingly, TA has also been shown to mitigate cognitive impairments in an AD mouse model. This study further investigates tannic acid’s mechanism of inhibition. The ability of tannic acid to prevent the formation of Aβ oligomers was first investigated. Aβ was solubilized in DMSO and diluted into PBS to initiate oligomerization. In the presence of a 10-fold excess of TA, Western blot analysis revealed that oligomers in the 37-75kDa range were absent. This molecular mass range translates to oligomer species of approximately 9 to 16 monomers. These species include the dodecamer, which has been suggested to be the primary toxic species in AD. The selective inhibition of this oligomer species was further probed using electron force microscopy and capillary electrophoresis. Additionally, cellular toxicity studies that utilize TUNEL staining to identify apoptotic cells correlate the absence of this oligomer species with altered Aβ neurotoxicity. Together, these studies provide insight into the inhibitory mechanism by which TA may exert its protective effect on AD.