Mapping How Cell Compartments Handle Fats in Alzheimer’s Disease

To understand how Alzheimer’s disease disrupts the way different compartments inside brain cells process, store, and transport lipids, with the goal of identifying new biological pathways that could be targeted for future treatments.

Fats (lipids) make up around 60% of the human brain and play an essential role in sustaining brain health. We now know that Alzheimer’s disease severely disrupts the cellular pathways responsible for making and organising these lipids. However, the precise details on how these pathways work, and what goes wrong with them during the disease, are poorly understood. To overcome this knowledge gap, our team will develop new methods to measure and understand changes in lipids inside brain cells. These findings could result in new therapeutic targets to treat the disease.

The most innovative aspect of this proposal is that it moves beyond measuring lipids at the level of whole cells and instead examines lipid metabolism within specific cellular compartments or organelles.
This is important because many critical lipid-processing events occur in distinct organelles, and whole-cell approaches miss biologically meaningful changes that are restricted to specific organelles.
The project also combines cutting-edge stem-cell models, organelle isolation and advanced lipidomics to create a functional platform that has not previously been available for studying Alzheimer’s disease.

Once complete, this study could reveal new mechanisms that explain how lipid metabolism contributes to brain cell dysfunction in Alzheimer’s disease. For research scientists, the project will establish a new experimental platform and organelle-specific lipid maps that can be used to study many neurological and metabolic disorders. For the general public, the long-term benefit is the potential identification of new therapeutic targets that may support the development of better treatments for Alzheimer’s disease and related dementias.