Mechanisms of Astrocyte-Derived Lipid Toxicity in Alzheimer’s Disease

Astrocytes are star-shaped cells that support the brain. They change their genes and functions when the brain is infected, injured or diseased, a process called “astrocyte reactivity.” Different types of reactive astrocytes have different roles in brain diseases like Alzheimer’s disease (AD). AD is caused by abnormal proteins and inflammation and abnormal functions of reactive astrocytes—including neurotoxicity. Inflammation is a double-edged sword: it can help or harm the brain. Inflammatory cells affect how astrocytes react to AD. One type of reactive astrocyte becomes toxic and harms neurons, the main cells of the brain; these toxic astrocytes release long-chain saturated fats that kill neurons. We found these astrocytes in diseased brain areas of AD human patients and in animal models of AD. They are not related to the genetics of AD patients, providing an exciting possibility that we can target them using novel future treatments that would not rely on patient predisposition. We want to find ways to stop astrocytes from making and releasing toxic fats and to protect neurons from these fats. This will help us understand how astrocytes work and how to treat AD more effectively.