Merin John

Alzheimer disease (AD) is a neurodegenerative disease marked by progressive loss of memory, cognitive function, judgement, and language capability. The beta-secretase-1 (BACE1) enzyme is crucial to the formation of amyloid plaques in the brain that characterize AD. The risk for AD has strong genetic correlations, and one of the genes known to increase risk for AD is ATXN1. Furthermore, lack of the functional ATXN1 gene has been associated with increased levels of Aβ peptides in tissue culture cells, which comprise the amyloid plaques found in AD patients. The mechanism by which this occurs is currently unknown, and this project aims to more clearly understand the relationship between ATXN1 and BACE1. Previous studies have proposed that ATXN1 may negatively regulate the transcription of BACE1, supporting my hypothesis that there will be increased expression of BACE1 in mice deficient for ATXN1(ATXN1 null / ATXN1-/- mice). This project evaluates this hypothesis by Western Blotting of protein lysates from the cortex and hippocampus of ATXN1 null and wild-type mice to compare BACE1 levels. My results show that normalized BACE1 protein levels are higher in ATXN1 null mice compared to wild-type mice in both the cortex and the hippocampus, supporting the hypothesis that ATXN1 negatively regulates expression of the BACE1 protein. In the future, this work may be complemented by further study comparing Aβ peptide and BACE1 mRNA levels in ATXN1 null and wild type mice.