Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology

Supervisor

Dr. Jane Rylett

Abstract

The primate specific 82-kDa choline acetyltransferase (ChAT) isoform is found in the nuclei of cholinergic neurons, with a disruption in the subcellular localization in aging and AD brain samples# The functional significance of this protein is poorly understood. Previous studies have revealed a potentially protective role for 82-kDa ChAT, mediated through a reduction in amyloid-!1-42 (A!1-42) release in APP/PS1 double transgenic primary cortical neurons. Here we examine the effect of 82-kDa ChAT expression in transgenic neurons, on the amyloidogenic processing of amyloid precursor protein (APP) and A! production. In this study we demonstrate 82-kDa ChAT transcriptionally increases golgi- localized "-ear-containing ARF-binding 3 (GGA3), a protein that traffics BACE1 to the lysosome for degradation. Increased GGA3 expression coincides with a reduction in BACE1 protein and activity levels, which may account for the reduction in A!1-42 production. These findings indicate a potential regulatory function of 82-kDa ChAT, specifically at the genetic level.


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