How the Brain's Support Cells Interact with Fats and Contribute to Alzheimer's Disease

This project’s aim is to uncover how Alzheimer’s disease–related changes in the brain’s support cells affect nerve cell function.

Astrocytes are cells that provide support to nerve cells in the brain. One of their jobs is to process and deliver fats, or lipids, to nerve cells to ensure their function and survival. In Alzheimer’s disease, astrocytes may fail to offer the appropriate lipid support, leaving neurons to become dysfunctional or even degenerate.

Till Zimmer, PhD, and his colleagues will take a first look at how different factors affect how astrocytes process lipids in dementia. They will use a lab model of Alzheimer’s disease to profile these effects.

The group also plans to assess how the newly identified astrocyte-processed lipids affect nerve cell function. This work is expected to add links to the chain connecting how the brain uses lipids and related processes in the development of Alzheimer’s disease.

Many common AD risk genes are implicated in lipid metabolism and astrocytes are critical for lipid metabolism in the brain. However, the exact astrocyte lipid profiles in the context of AD pathology are not known. For the first time, we will define astrocyte lipids in AD models and identify mechanisms regulating astrocytic lipids in disease. We will use the newly identified lipids to study how they influence neuronal function, which could help to better understand the links between AD and lipid metabolism.

First, the study will provide a valuable resource detailing various lipid modification in astrocytes, which could be used in subsequent studies to better understand lipid-related mechanisms in AD and related dementias. Second, we will employ translatomics to integrate with lipid analyses to resolve the interplay between lipids and their regulators. Third, by examining astrocyte lipids and their regulatory factors and effects on neurons, the study will contribute to a better understanding of these mechanisms and their potential use as novel avenues for drug and biomarker development.