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Updated: May 29, 2025

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
Published on: October 17, 2015
Valosin-containing Protein is Cargo in Amyloid Precursor Protein Extracellular Vesicles
Yue Lu1, Mohammad Abdullah1, Liam R Healy1
1Department of Pharmacology, Physiology & Neuroscience New Jersey Medical School, Brain Health Institute, Rutgers, The State University of New Jersey, 185 South Orange Ave, Newark, NJ, 07103, USA.
Abstract:
The Amyloid Precursor Protein (APP), a genetic cause of Alzheimer's disease (AD), is a type-I transmembrane protein that is metabolized by proteolysis in the endolysomal system. APP and its metabolites are secreted by cells in extracellular vesicles (EVs). To study the function of APP-containing EVs, we isolated App-EVs from rat primary neuronal conditioned media and proteomic analysis identified the Valosin-containing protein (Vcp) as molecular cargo. Pharmacological modulation of Vcp activity was found to alter App processing and global EV secretion in rat primary neurons. AD-associated knock-in App mutations were found to alter the abundance of App-EVs and the trafficking of App metabolites within App-EVs, in a manner related to the epitopes generated by the nonamyloidogenic processing of App. The presence of Vcp suggests a role for App-EVs in the clearance of protein aggregates.
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