2023 Alzheimer's Association Research Grant (AARG)

FAM222A ad Tau pathology in Alzheimer's disease

How does a risk gene for Alzheimer’s impact the accumulation of harmful proteins in the brain?

Jingjing Liang, Ph.D.
University of Arizona
Tucson, AZ - United States

Background

Scientists have identified several genes that increase the risk of Alzheimer’s. Risk genes increase the likelihood of developing the disease but do not guarantee it will happen. It is likely that there are other genetic and environmental factors that contribute to Alzheimer’s risk that have not yet been identified.

Recent studies have identified an Alzheimer’s risk gene named FAM222. A variation of this gene results in the production of a protein called Aggregatin. This protein appears to contribute to the formation of beta-amyloid plaques, a hallmark brain change associated with Alzheimer’s. However, the way Aggregatin impacts the build-up of the tau protein, another hallmark brain change associated with Alzheimer’s, is not known.
 

Research Plan

Dr. Liang and colleagues will study the functions of Aggregatin using mice genetically engineered to lack the Aggregatin protein. To study the impact of Aggregatin on tau, the researchers will cross the mice lacking Aggregatin with genetically engineered Alzheimer’s-like mice to create mice that develop Alzheimer’s-related brain changes without Aggregatin. The team will collect a variety of data from the mice, including the results of behavioral tests, measures of nerve cell health and brain inflammation, and measures of harmful tau build-up. Dr. Liang and colleagues will investigate the biological mechanisms underlying how Aggregatin may interact with tau, as well as Aggregatin’s impact on brain inflammation and nerve cell health. The research team will also study how Aggregatin, tau clumps, brain inflammation, and nerve cell death overlap in specific areas of the brain over time.

Impact

The findings may add to our understanding of how genetic risk factors may contribute to Alzheimer’s. If successful, the results may shed light on how Aggregatin may impact the brain changes associated with Alzheimer’s.