2023 Alzheimer's Association Research Grant (AARG)
Decoding Epigenetic Scarring in Alzheimer’s disease
How might virus exposure influence an individual’s risk of developing cognitive symptoms in Alzheimer’s?
Huihui Fan, Ph.D.
The University of Texas Health Science Center at Houston
Houston, TX - United States
Background
Some research suggests that exposure to certain viruses may increase an individual’s risk of developing brain diseases later in life. This increased risk may persist for years following a person’s exposure to these viruses. Given the widespread nature of COVID-19, several datasets now exist that include biological samples collected from individuals who experienced this virus infection. These datasets offer a unique opportunity to investigate genetic changes that occur following virus exposure and how they might influence disease risk.
The body turns genes “on” or “off” in response to stimuli, including virus infections. It does this using epigenetic modification, or the chemical modification of genetic material (DNA). Epigenetics can help researchers measure gene levels and understand an individual's biological response to virus infections. Clinicians can also measure molecules in the blood, known as metabolites, to help study viral infections.
Research Plan
Dr. Huihui Fan and colleagues will utilize both epigenetic and metabolic data from individuals who had COVID-19 and look for associations with cognitive symptoms. This multi-layered approach will help Dr. Fan determine how exposure to COVID-19 might lead to lasting changes in an individual's genes, known as epigenetic “scarring,” which could underlie their risk of developing brain diseases, including Alzheimer’s.
Dr. Fan’s team will study datasets from 50 individuals who had severe COVID-19 for a long time (long COVID). The researchers will analyze epigenetic and metabolic data collected from these individuals over the course of their disease process, and track any changes that occur. First, they will identify any connection between an individual's genetic changes and the metabolites found in their blood. Then, the researchers will look for further connections with an individual’s cognitive symptoms. As a last step, the researchers will compare their findings to genetic data from individuals who have Alzheimer’s. This will allow Dr. Fan to understand which kinds of epigenetic “scars” occur during or following COVID-19, and whether any might overlap with epigenetic changes that occur in Alzheimer’s.
Impact
Results from this study will provide insight into how genes are modified following COVID-19 infection, and how this might contribute to cognitive symptoms often seen in Alzheimer’s.