Date of Award


Degree Type


Degree Name

Master of Science




Dr. Jane Rylett

Second Advisor

Dr. Marco Prado

Third Advisor

Dr. Frank Beier


The 82-kDa isoform of choline acetyltransferase (82-ChAT) is unique to primates and is found in cholinergic cell nuclei. The functional significance of this protein is not well understood. Previous studies showed that nuclear 82-ChAT levels decrease with advancing age, and this is accelerated in Alzheimer’s disease (AD). The present studies examined the effect of 82-ChAT on amyloid precursor protein (APP) metabolism and amyloid-P (Ap) production. Levels of enzymes involved in processing of APP were examined in human SH-SY5Y neuroblastoma cells and in primary neuronal cultures prepared from cerebral cortex of embryonic APP/PS1 double transgenic mice that serve as a model of AD. A significant amount of APi^2 was released into cell culture media from neurons cultured from transgenic mice for 8 DIV, and this was associated with an elevation of total APP levels rather than changes in levels of APP processing enzymes. Upon expression of 82-ChAT, a 20% reduction in AP-m2 release was found when compared to GFP-expressing control neurons. This was associated with a significant reduction in the protein but not mRNA of the p-secretase BACE1, indicating that 82-ChAT may alter proteins involved in post-translational modification and regulation of BACE1. These studies have important implications for AD pathology and broaden our understanding of the function of 82-ChAT proteins.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.