Impaired RNA Editing as A Cause of Neuroinflammation in Alzheimer's Disease

Alzheimer’s disease is a serious brain disorder that leads to memory loss and cognitive decline, affecting millions of people worldwide. While it is clear that genetics plays a crucial role in the onset and progression of the disease, the specific mechanisms remain to be fully understood. Recent research suggests that the brain’s immune cells, specifically microglia, can become overactive in Alzheimer’s, triggering inflammation that damages brain neurons and exacerbates cognitive decline. Our project aims to explore how certain genetic changes might lead to this overreaction through a process known as RNA editing. This process is essential for maintaining cellular homeostasis and preventing the immune system from attacking the body’s own cells. Normally, an enzyme involved in RNA editing modifies RNA molecules to ensure proper cellular function. However, when this editing process fails, microglia may mistakenly detect a threat and initiate an immune attack against healthy brain tissue. This erroneous immune response is driven by a molecule that senses abnormal RNA and activates inflammatory pathways, further contributing to neuronal damage. To test this hypothesis, we will study brain-like cells derived from human stem cells in the laboratory, allowing us to observe the effects of altered RNA editing on microglial activity. Additionally, we will reduce the activity of the RNA editing enzyme in mice to investigate how this impacts brain health and cognitive function. Our findings could provide valuable insights into the role of RNA editing in Alzheimer’s disease and inform potential therapeutic strategies.