2023 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

Cortico-Hippocampal Dysfunction in the Progression of Alzheimer's disease

How do nerve cells in the brain change over the course of Alzheimer’s progression?

Melissa Hernandez Frausto, Ph.D.
New York University Grossman School of Medicine
New York, NY - United States

Background

Glutamate is a chemical compound that helps nerve cells communicate with one another through electrical signals. Studies by Dr. Melissa Hernández-Frausto and others have shown nerve cells that use glutamate to communicate may be particularly vulnerable in  Alzheimer’s. These nerve cells can become overactivated, particularly in brain regions important for Alzheimer’s including the entorhinal cortex (a brain region that functions as a center for the formation of memories and object recognition, among other tasks) and hippocampus (a brain region important for learning and memory).

Research Plan

Now, Dr. Hernández-Frausto and colleagues are working to understand when, during the course of Alzheimer’s progression, nerve cells that use glutamate become overactivated. The researchers will use genetically modified Alzheimer’s-like mice, including mice of different ages to allow comparisons between early and late stages of disease. They will implant a small window over the brain of the mice to allow visualization of certain brain regions, then use specialized brain scan techniques to monitor the activity of nerve cells that use glutamate. The researchers will later analyze brain tissue samples for signs of nerve cell damage.

Dr. Hernández-Frausto’s team will then use a specialized technique, called optogenetics, which involves directing precisely controlled pulses of light at specific nerve cells in the brain to activate them. The researchers will determine whether activating nerve cells that use glutamate before disease onset might protect Alzheimer’s-like mice from brain damage.

Impact

Results from this study may provide a timeline of when certain nerve cells become damaged during disease. This study will also test whether an intervention in the earliest stage of disease might help prevent or slow disease progression.