Identifying the Cause of Protein Accumulation in Alzheimer's Disease

Matthew Rexroad*, Janelle Chuah, and David M. Smith

Department of Biochemistry, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26505

Presentation Category: Biological & Biochemical Sciences (Poster Presentation #109)

Student’s Major: Biochemistry

Many neurodegenerative diseases such as Alzheimer’s are typically characterized by the buildup of proteins such as amyloid-beta and tau. Accumulation of proteins occurs both intracellular and extracellular, affecting neuronal functions such as synaptic plasticity, memory formation, and ultimately loss of neuronal connections causing cell death. Normally, intracellular proteins are degraded by a molecular machine called the proteasome Within areas of the brain affected by Alzheimer's, both in clinical samples and animal models, proteasome function has found to be significantly lower compared to healthy brains. Previous in vitro studies showed that the proteasome can be impaired by neurodegenerative associated proteins such as amyloid-beta and huntingtin when they fold in a particular confirmation. The inhibitory confirmation is recognized by the A11 antibody. The purpose of this study is to develop an ELISA protocol that will eventually be used to confirm the clinical relevance of A11 impairment of the proteasome in Alzheimer’s. The goal is to show proteasomes bound A11 oligomers in clinical samples. Results of this study could have implications in identifying the proteasome as a pharmaceutical target for Alzheimer’s.

Funding: National Institute of Health (NIH)

Program/mechanism supporting research/creative efforts: WVU's Research Apprenticeship Program (RAP) & accompanying HONR 297-level course