2023 Alzheimer's Association Research Grant (AARG)
Single cell atlas of human resilience factors against Alzheimer's dementia
Do specific genes protect brain function in certain individuals with hallmarks of Alzheimer’s?
Jessica Rexach, M.D., Ph.D.
University of California
Los Angeles, CA - United States
Background
Two of the hallmark brain changes in Alzheimer’s are the accumulation of beta amyloid in the form of plaques and tau in the form of tangles. The formation of plaques and tangles have been shown to negatively impact nerve cell function and lead to cognitive decline. Recent studies have found that certain individuals, classified as “non-demented with Alzheimer’s neuropathology” (NDAN), develop plaques and tangles in the brain but do not experience significant cognitive loss. However, the factors driving this “cognitive resilience” are not known.
Dr. Jessica Rexach believes that a specific region in the brain called the entorhinal cortex (ERC), a brain region that functions as a center for the formation of memories and object recognition, among other tasks, may be key to uncovering why certain individuals have cognitive resilience.
Research Plan
Dr. Rexach and colleagues will use single-cell whole genome-sequencing to study genes in individual cells within the brain that may be linked to cognitive resilience. The researchers will do this by studying brain tissue from individuals who had NDAN or Alzheimer’s, as well as cognitively unimpaired individuals. Since previous studies have demonstrated that the ERC may be protective in preserving cognitive health, they will focus on differences in cells within the ECR between the groups to identify genes associated with cognitive resilience.
Impact
If successful, the results of this study may shed new light on the mechanisms that protect against cognitive decline and could lead to novel methods of preserving cognitive health in individuals with Alzheimer’s.