2024 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)
Deciphering Alzheimer's Astro-Neuron Energy Link at Micro-Niche resolution
How does metabolism differ between unique types of brain cells in Alzheimer’s?
Julio Leon Incio, Ph.D.
The Regents of the University of California, San Francisco
San Francisco, CA - United States
Background
Metabolism is a process during which the body breaks down nutrients into energy. During this process, the body produces compounds called metabolites, which help the body maintain normal functions. In the brain, metabolites help maintain both energy levels and connections or communications across wide-scale “networks” of brain cells, which in turn promote memory and other cognitive functions. Studies have shown that one such network, composed of nerve cells (neurons) and astrocytes (the “support” cells of the nervous system), becomes dysfunctional in Alzheimer’s and may contribute to cognitive decline. However, it is unknown how metabolite activity between neurons and astrocytes and Alzheimer’s progression are related.
Research Plan
For their studies, Dr. Julio Leon Incio and colleagues aim to identify the metabolic pathways within the astrocyte-neuronal network that are altered in Alzheimer’s. They will do this using an advanced imaging technique called spatial transcriptomics (the study of where in the brain certain genes are turned “on” or “off”) to measure the metabolism-related genes that are turned “on” or “off” in astrocytes and neurons in brain tissue from individuals who had Alzheimer’s. Next, the researchers will measure changes in specific metabolites in the same brain tissue using spatial metabolomics (a technique that measures all metabolites, or nutrients, within a brain region). They will then identify which metabolism-related genes and metabolites in astrocytes and neurons are associated with amyloid plaques and tau tangles (two of the hallmark brain changes in Alzheimer’s) in each sample. Lastly, the team will use genetically engineered Alzheimer’s-like mice to examine the relationship between astrocyte-neuronal networks, metabolism, and APOE variants (one of the genetic risk factors for Alzheimer’s).
Impact
Results of this study could improve our understanding of the biological mechanisms that drive altered brain metabolic activity in Alzheimer’s.