The mechanism and significance of the synaptogenic activity of amyloid precursor protein

Michael Smith Foundation for Health Research/The Pacific Alzheimer Research Foundation Post-Doctoral Fellowship Award

Amyloid Precursor Protein (APP) is a cell surface protein that has been mostly studied in the context of Alzheimer’s disease. Much about its normal function remains unknown. APP can cause connections to form between brain cells by an unknown mechanism. We believe this happens through an interaction with synaptic organizing proteins (organizers).

This project will investigate the possibility that APP forms synapses by interacting with major organizers in the brain, namely neurexins and receptor protein tyrosine phosphatases (RPTPs).

To test this, we will use a combination of cell cultures and mouse models. We will test whether APP binds to neurexins and RPTPs and whether binding to these organizers is required for the connection-forming activity of APP. We will also compare brain cell connections in normal mice to those in mice that express an altered form of APP that cannot bind to organizers.

This study may shed light on the function of APP through detailing how it can help form connections between brain cells. If defects in connections between brain cells contribute to neurodegeneration in Alzheimer’s disease, these results could shed light on the mechanisms behind that as well.