Role of ABCA1 in brain cholesterol metabolism and brain function

Although the brain accounts for only 2 per cent of total body weight, it contains almost 25 per cent of total body cholesterol. This cholesterol is critical to healthy functioning in the brain, and plays an important role in learning. Abnormalities in the synthesis of brain cholesterol are associated with several devastating diseases, including Alzheimer’s and Huntington’s. However, not much is known about how the central nervous system regulates the metabolism and movement of cholesterol in the brain. Two-thirds of brain cholesterol is located in myelin, an insulating layer that surrounds the nerve fibers of brain cells where it supports transmission of signals between neurons across connections called synapses. Cholesterol also helps repair neurons. Although the synthesis of cholesterol occurs at a high level in the developing brain, it declines significantly in the adult brain. Consequently, the brain must rely on efficient transport and recycling to meet its need for cholesterol in the brain cells. Dr. Joanna Karasinska is investigating whether ABCA1, a major cholesterol transporter in the brain, controls the metabolism of cholesterol and how this affects brain function. This knowledge could lead to new therapies for neurological disorders associated with a cholesterol imbalance in the brain, and for the repair of neurons following a brain injury.