2024 Alzheimer's Association Research Fellowship (AARF)

Investigating aberrant cellular mechanics as early event of tau pathology

What are the earliest changes that occur when tau accumulates in the cell?

Martha Foiani, Ph.D.
University College London
London, United Kingdom

Background

Tau is a protein that helps maintain the structure of brain cells. In Alzheimer’s and other brain diseases, the shape of tau protein becomes modified or “misfolded,” a change that may contribute to tau tangles (a hallmark of these diseases) and subsequent nerve cell damage. Brain diseases that have high levels of the modified tau are called “tauopathies”.
 
Studies have shown that some of the earliest changes that occur when tau begins to build up in the cell. Specifically, tau builds up in the area of the cell that is responsible for providing the cell’s structure for shape and internal organization area and protects the cell from stress. Unfortunately, injuring this part of a cell can have further negative effects including damage to the protective layer of the cell’s “control center” that contains all the cell’s genetic material. This damage to would explain many of the tau-related changes other studies have previously reported.

Research Plan

Dr. Foiani and colleagues will investigate the earliest changes that occur in cells following tau build up. Initially, researchers will measure how tau accumulation changes the “stiffness” of the cell’s structure and shape. Next, the research team will use a technique called electron microscopy, a way of taking very detailed pictures of the insides of cells, to learn how tau accumulation affects the cytoplasm and the nuclear envelope. Finally, Dr. Foiani and team will disrupt various processes in the cell to see if they can prevent the changes that occur in the cell in the presence of tau build up. 

Impact

If successful, this study will help researchers better understand the earliest changes that occur when tau accumulates in the brain, and identify strategies to potentially reverse or slow these processes down.