Fats are really important for our brains, which are made up of about 60% fat, making it the fattiest organ in our body. Therefore, the regulation of fats is really important, and so it may not come as a surprise that changes in processes linked with fat metabolism and regulation are altered in Alzheimer’s. In this project, Dr Huiliang Li sets out to explore the links between fats, key support cells in our brains and changes seen in Alzheimer’s.
The most well-known risk gene for Alzheimer’s is the ApoE4 gene, and the protein produced by this gene is involved with the regulation and processing of lipids such as cholesterol within our cells, suggesting that these processes may be linked with the disease. Dr Li has previously found that manipulating a protein called ACAT1 can alter cholesterol levels and that this can reduce the build-up of key Alzheimer’s proteins in the brains of mice with features of Alzheimer’s. In our brains, the majority of cholesterol is made in cells called oligodendrocytes, which insulate our nerve cells like the plastic coating on wires, helping to speed up the transmission of messages along a nerve cells length. Looking at cholesterol, ACAT1, oligodendrocytes and Alzheimer’s-related changes together, Dr Li is putting pieces of the jigsaw puzzle together to improve our understanding around these key changes. If ACAT1 is revealed to play a key role in linking cholesterol and Alzheimer’s-related changes, this protein could be targeted by future treatments hoping to slow down the damage occurring in the brain in Alzheimer’s disease.
Dr Li and his team are working with mice bred to have features of Alzheimer’s disease, and will first measure how cholesterol levels change in these mice as they age and compare this with regular older mice. As cholesterol is mainly made by support cells called oligodendrocytes, they will then focus on these cells in particular. By measuring the levels of a protein called ACAT1 in oligodendrocytes, the team will explore whether any changes in cholesterol levels during ageing may be being driven by changes in ACAT1. To understand the links between ACAT1 and Alzheimer’s, they will study mice that have been bred to have features of Alzheimer’s disease but no ACAT1 protein, and compare these mice with ones bred just to have features of Alzheimer’s. Looking at oligodendrocytes and the characteristic build-ups of Alzheimer’s proteins, the team can reveal whether ACAT1 plays a key role linking cholesterol and Alzheimer’s disease.
Dr Huiiang Li
University College London
1 August 2017 - 31 July 2018
Full project name
Cholesterol esters in oligodendrocytes and the implications for Alzheimer’s disease