Modulation of APP Trafficking and Abeta Production

Principal Investigator
Guojun Bu, PhD
Hong Kong University of Science and Technology
Hong Kong, China
About the Research Project
Program
Award Type
Standard
Award Amount
$300,000
Active Dates
April 01, 2006 - March 31, 2008
Grant ID
A2006012
Summary
Amyloid β-peptide (Aβ) accumulation in the brain is a pathological hallmark of Alzheimer’s disease (AD). Recent studies have shown that aggregated forms of Aβ is toxic to neurons and contribute to memory loss in AD. The toxic Aβ is derived from sequential cleavage of a larger protein called the amyloid precursor protein, or APP. Increased APP cleavage can directly cause AD. APP is a dynamic molecule that moves among different compartments within cells. The general hypothesis is that APP cycling between cell surface and inside the cells increases its chance to be cleaved to Aβ. Dr. Bu has identified three important molecules called LRP, LRP1B, and sorting nexin 17 (SNX17), each interacts with APP and modifies its cycling speed. Specifically, the preliminary studies found that LRP and SNX17 facilitate and LRP1B inhibits APP cycling. The goal of this proposal is to analyze in brain-derived neurons whether their effects on APP cycling also translate into changes in Aβ production. If the results are confirmed, drugs can be designed to increase LRP1B levels or decrease LRP and SNX17 levels to benefit AD patients.
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