2018 Alzheimer's Association Research Grant (AARG)

Investigating the Role of Neuronal Exosomes in Alzheimer's Disease

How do nerve cells remove harmful proteins during Alzheimer’s?
 

Jason Shepherd
University of Utah
Salt Lake City, UT - United States

Background

During Alzheimer’s harmful proteins including beta-amyloid and tau, can aggregate inside nerve cells. Nerve cells use many strategies to remove these harmful proteins. One way nerve cells clear harmful proteins is by enclosing them in tiny, fluid-filled bubbles that bud off from the nerve cell membranes. These bubbles, called exosomes, can help transport harmful proteins out of the nerve cells. However, these exosomes filled with harmful protein can be picked up by a healthy nerve cell, resulting in the spread of harmful proteins.
 
Dr. Jason Shepherd and colleagues have recently discovered that a nerve cell protein, called Arc, is also found inside these bubbles. Arc is involved in many nerve cell functions, and may also help control how harmful proteins are removed from nerve cells during Alzheimer’s.
 

Research Plan

In the present study, Dr. Shepherd and colleagues will determine the role of Arc in transporting beta-amyloid precursor (APP) (beta-amyloid is a small piece of the larger protein APP) and tau proteins via exosomes. The researchers will tag APP and tau with light emitting molecules to follow them around inside nerve cells. Using high resolution microscopes Dr. Shepherd will study how APP and tau protein travel within and out of nerve cells in the presence and absence of Arc. Dr. Shepherd will also determine if altering Arc affects protein plaque and tangle formation- two hallmark brain changes in Alzheimer’s- inside the nerve cells.
 

Impact

This study could provide new information about how exosomes may help harmful proteins spread between nerve cells during Alzheimer’s. Since exosomes can be measured in biological fluids (such as blood and fluid surrounding the spinal cord and brain), they may also serve as biological markers to identify a person’s risk of Alzheimer’s or therapeutic targets to delay or slow Alzheimer’s progression.