2024 Alzheimer's Association Research Fellowship (AARF)
Decoding the signaling contexts underlying human glial cell-state landscape
How does gene activity change in different types of brain cells during normal aging and in Alzheimer’s?
Natacha Comandante-Lou, Ph.D.
Columbia University Irving Medical Center
New York, NY - United States
Background
Researchers have long understood that age is the strongest risk factor for Alzheimer’s and other dementia. Aging involves many complex factors, including changes in genes, proteins, metabolism, and immune system function – all of which can impact one’s risk of developing Alzheimer’s and the progression of the disease. Additionally, different types of cells in the brain undergo changes during normal aging and in Alzheimer’s. Recent studies have shown that glial cells, including astrocytes (the “support cells” of the nervous system) and microglia (the primary immune cells of the brain) become overly active in Alzheimer’s, creating a unique “ecosystem” in the brain that drives Alzheimer’s progression. However, the precise mechanisms that shift the brain’s microglia-astrocyte ecosystem from healthy aging to Alzheimer’s are unknown.
For their studies, Dr. Natacha Comandate-Lou and colleagues aim to identify the cellular signals and pathways that drive the microglia-astrocyte ecosystem changes observed in Alzheimer’s compared with normal aging.
Research Plan
Dr. Comandate-Lou and the team will use an advanced sequencing technique called spatial transcriptomics (the study of where in the brain certain genes are turned “on” or “off”) to study gene activity differences in microglia and astrocytes. They will perform this technique on brain tissue samples collected from individuals who had Alzheimer’s as well as cognitively unimpaired individuals to identify changes in the microglia-astrocyte ecosystem that are specific to Alzheimer’s. Next, the researchers will use metabolomics (a technique that measures all metabolites, or nutrients, within a cell) to examine changes in gene activity with altered metabolic pathways in astrocytes that are associated with the astrocyte-microglia ecosystem in Alzheimer’s and normal aging.
Impact
Results of this study could improve our understanding of the biological mechanisms that drive astrocyte and microglia changes that are observed in Alzheimer’s.