2023 Alzheimer's Association Research Fellowship (AARF)
Molecular mechanisms and effects of Alzheimer’s-related lipid dysregulation
How do changes in fats found in astrocytes contribute to Alzheimer’s?
Till Zimmer, Ph.D.
Weill Medical College of Cornell University
New York, NY - United States
Background
Alzheimer’s is associated with hallmark brain changes including the accumulation of the proteins beta-amyloid and tau into abnormal plaques and tangles, respectively. Alzheimer’s is a complex disease and there are other brain changes that occur, and may be linked to the plaques and tangles. One additional brain change includes the build-up of lipids (fats) in brain cells.
Brain cells (in particular, nerve cells) need lipids for energy and for maintaining their structures. As a result, the process by which fat is produced and transported to these cells is vital for the proper function of the brain. Nerve cells receive fats from “helper” cells in the brain called astrocytes. Scientists have found that lipids can accumulate abnormally in the brain, possibly leading to the build-up of the proteins tau and beta-amyloid.
The amount and type of lipids found in various brain cells can dramatically impact the cell's function. Of particular interest in Alzheimer’s is how these lipids can change inflammation, or the cell’s response to debris or damage, and how it spreads that response to other cells. This project aims to identify changes in terms of the lipids and inflammation in the astrocytes.
Research Plan
Zimmer and colleagues will then use brain tissue from genetically engineered Alzheimer’s-like mice to identify changes in lipids through disease progression, in particular focusing on changes in astrocytes and near buildups of amyloid. Additionally, they will examine changes to inflammation that are able to also impact lipids. Finally, they will look at how this inflammation leading to lipid changes can alter astrocyte ability to help maintain proper neuron function.
Impact
This project has the potential to increase our understanding of the connection between amyloid, inflammation, and lipid metabolism in Alzheimer’s. This can help identify new targets for drug development to treat Alzheimer’s.