2024 Alzheimer's Association Research Grant to Promote Diversity (AARG-D)

Bi-phasic microtubule-based mechanisms and therapies for tauopathies

Are there multiple mechanisms by which tau accumulation promotes nerve cell loss?

Liang Qiang, M.D., Ph.D.
Drexel University
Philadelphia, PA - United States

Background

Tau is a protein that helps maintain the structure of healthy brain cells. However, the shape of tau protein can become modified or “misfolded,” leading to the accumulation of tau tangles, one of the hallmark brain changes in Alzheimer’s and other brain diseases. Accumulation of tau tangles can impact nerve cell communication and lead to nerve cell damage and death. Brain diseases believed to result from tau tangles are called “tauopathies”. Studies have found that different types of tau tangles can lead to nerve cell damage by multiple mechanisms. 

Dr. Liang Qiang and colleagues believe these differences may be due to how tau interacts with axon microtubules, or proteins that provide support to specialized structures in nerve cells called axons, which help cells communicate with each other.

Research Plan

For their studies, the researchers will use a specialized type of stem cell collected from adult human tissue called induced pluripotent stem cells (iPSCs). These are cells that can be “programmed” into any type of cell in the human body, including nerve cells, and grown in a laboratory dish. The iPSCs used for this study will have different genetic variations in the gene that provides instructions for making the tau protein, which will result in unique forms of tau tangles. The team will measure how each tau variation physically interacts with axon microtubules. Lastly, the team will examine the amount of nerve cell damage associated with each tau variation.

Impact

The results of this project may help us better understand the mechanisms that lead to nerve cell damage in tauopathies.