2016 Alzheimer's Association Research Fellowship (AARF)

Characterization of Human AD Brain-Derived Exosomes on Tau Propagation

How do cellular transport pathways contribute to the movement of abnormal tau protein throughout the brain in Alzheimer’s disease?

Annina Maria DeLeo, Ph.D.
Boston University, B U Medical Campus
Boston, MA - United States

Background

Tau is a protein that normally helps to maintain nerve cell structure and transport nutrients throughout the cell. In Alzheimer’s disease, tau becomes abnormally modified and can form tau tangles in the brain, a hallmark of the disease. Recent evidence suggests that abnormal tau protein can spread from one nerve cell to the next, possibly contributing to the progression of brain changes associated with Alzheimer’s disease. However, the mechanisms that underlie the accumulation and movement of abnormal tau in the brain are not well understood.

All cells are enclosed in a barrier known as the cell membrane. Small pieces of this membrane called exosomes are sometimes released from the cell and used to transport proteins and other molecules between cells. More research is needed to determine if exosomes carrying abnormal tau may lead to its movement throughout the brain during the progression of Alzheimer’s disease.

Research Plan

Annina Maria DeLeo, Ph.D., and colleagues have proposed a series of studies to determine how exosomes may contribute to the spread of tau tangles in the brain. They will isolate exosomes from the brain tissue of people with and without Alzheimer’s disease to look for differences in the levels of tau and other proteins associated with nerve cell damage. The researchers will also study how exosomes promote the spread of abnormal tau between nerve cells in the brain of Alzheimer’s-like mice. Dr. DeLeo and colleagues hope to identify the proteins in the exosome that allow it to bind to other nerve cells and spread tau tangles.

Impact

This research could improve our understanding of how exosomes in the brain impact the development of Alzheimer’s and other neurodegenerative diseases. These studies could also identity new targets for drug treatments aimed at blocking the spread of abnormal tau protein in the brain to help slow or prevent disease progression.

This project was made possible by the Dale Schenk Alzheimer's Association Research Roundtable Award.