APP C-Terminal Fragment: Effect on Cognition and Aβ

For the past two decades, researchers in Alzheimer’s disease (AD) field have focused on the neurotoxicity associated with Aβ peptide production and accumulation. Amyloid beta (Aβ) is a small peptide molecule generated from cleavage of amyloid precursor protein (APP). Our proposed studies will explore the APP molecule as a whole cellular component that could affect brain function and memory processing. We will focus more specifically on the intracellular fragment of APP that could initiate signaling events. We aim to deliver a small peptide fragment to the brain of familial AD mouse models using a viral strategy. The overall goal is to develop novel rational therapeutics aimed at preserving cognitive function and reducing Aβ burden in those suffering from AD.

Our research will test the hypothesis that production of an intracellular fragment originating from APP could rescue memory decline in AD mice. Viral injection in the brain will facilitate the overproduction of this fragment. We will consider the likelihood that viral transduction of this short peptide could attenuate Aβ production and deposition in AD mice, and rescue their memory function. We will characterize the mechanisms underlying these changes.

Grantee institution at the time of this grant: University of Chicago