2024 Alzheimer's Association Research Grant to Promote Diversity (AARG-D)

Microglia-Mediated Mitochondrial Calcium Signaling in Alzheimer's Disease

How do changes in calcium levels in the brain’s immune cells contribute to Alzheimer’s?

Pooja Jadiya, Ph.D.
Wake Forest University Health Sciences
Winston-Salem, NC - United States

Background

Mitochondria are specialized structures inside cells that produce energy. Inside the mitochondria are several molecules that support this energy-production process, including calcium. Not only is calcium essential for energy production, but studies have shown that how calcium moves into and out of the mitochondria plays an important role in overall brain health and may be linked to Alzheimer’s and other dementias. 

Researchers have found one of the ways calcium levels are associated with Alzheimer’s is through its impact on microglia, or the brain’s immune cells. In preliminary studies, Dr. Pooja Jadiya and team have identified a specific protein, called the mitochondrial sodium/calcium exchanger (NCLX), that transports calcium within the mitochondria, and is elevated in the microglia of individuals who had Alzheimer’s.

Research Plan

For their project, Dr. Pooja Jadiya and colleagues will study the mechanisms linking NCLX and mitochondria impairment in microglia with Alzheimer’s. They will do this using genetically engineered Alzheimer’s-like mice that either have or do not have the NCLX protein in the microglia. The researchers will perform behavioral and cognitive tests on the mice to examine whether high levels of NCLX impact Alzheimer’s progression. Next, the team will measure mitochondrial activity, neuroinflammation, nerve cell signaling, and brain metabolism in these mice to examine the mechanisms by which NCLX may contribute to Alzheimer’s. 

Impact

The results of this project may shed new light on the mechanisms linking changes in mitochondrial calcium with the hallmark brain changes in Alzheimer’s. The findings may also identify new therapeutic targets for restoring mitochondria function in Alzheimer’s.