Targeting APP Intracellular Fragment to Improve Memory and Reduce Aβ Burden in AD

Angèle Parent, PhD
University of Chicago (Chicago, IL)
Year Awarded:
2017
Grant Duration:
July 1, 2017 to September 30, 2020
Disease:
Alzheimer's Disease
Award Amount:
$300,000
Grant Reference ID:
A2017443S
Award Type:
Standard
Award Region:
US Midwestern
Angèle Parent, PhD

APP C-Terminal Fragment: Effect on Cognition and Aβ

Summary

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.

Details

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.

About the Researcher

Dr. Angèle Parent is a Research Associate Professor in the Department of Neurobiology at the University of Chicago. Dr. Parent is a trained neurophysiologist who has a longstanding interest in AD with special emphasis on the mechanisms involved in memory storage. Her research seeks to clarify the protein machinery involved in memory formation and consolidation under normal and pathological conditions, focusing on synaptic transmission and brain plasticity. Dr. Parent graduated from The University of Montréal and pursued a postdoctoral training at The Johns Hopkins University. She has dedicated more than 25 years to investigate on basic mechanisms that affect memory function in AD patients. Her laboratory has successfully combined electrophysiological expertise with molecular and cell biology approaches to better understand complex mechanisms underlying the memory process in mouse models of AD. Dr. Parent is fully committed to making a difference in the lives of those who are afflicted by this devastating disease.

Personal Story

Dr. Angèle Parent and Dr. Gopal Thinakaran, her collaborator and husband, met at The University Johns Hopkins during their postdoctoral training. They joined the Department of Neurobiology at the University of Chicago in February 1999. Since then, they have fully dedicated themselves professionally to AD research and personally to their three children: Abigaël (16 years old), Daphné (11 years old), and Cédric (9 years old). As an annual addendum to her busy schedule, Dr. Parent loves to communicate her passion for the brain to children during the Society for Neuroscience Brain Awareness week. She takes that opportunity to teach the youngsters about the importance of the brain in our daily activities, how it looks, how it works and how to protect it. She looks forward to watching some of these youths become the next generation of neuroscientists and witnessing their quest to find new brain discoveries that will help ease people affected by devastating brain disorders such as Alzheimer’s disease. She is extremely grateful to the BrightFocus Foundation and its donors for the honor of being awarded an ADR grant to pursue her commitment to finding a cure for Alzheimer’s patients.

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 PubMed Icon Google Scholar Icon

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 PubMed Icon Google Scholar Icon

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