APP C-Terminal Fragment: Effect on Cognition and Aβ
Principal Investigator
Project Goals
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.
Project Summary
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.
Publications
Deyts C, Clutter M, Pierce N, Chakrabarty P, Ladd TB, Goddi A, Rosario AM, Cruz P, Vetrivel K, Wagner SL, Thinakaran G, Golde TE, Parent AT. APP-Mediated Signaling Prevents Memory Decline in Alzheimer's Disease Mouse Model. Cell Rep. 2019 Apr 30;27(5):1345-1355.e6. doi: 10.1016/j.celrep.2019.03.087. PubMed PMID: 31042463; PubMed Central PMCID: PMC6508668 
Deyts, C., Clutter, M., Pierce, N., Chakrabarty, P., Ladd, T. B., Goddi, A., ... & Thinakaran, G. (2019). APP-Mediated Signaling Prevents Memory Decline in Alzheimer’s Disease Mouse Model. Cell Reports, 27(5), 1345-1355. PMID: 31042463 DOI: 10.1016/j.celrep.2019.03.087
First published on: July 26, 2017
Last modified on: April 28, 2024