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2017 Grants - DeStrooper
Dissecting the Role of Human Astroglia in Alzheimer’s Disease
Bart DeStrooper, M.D., Ph.D.
Flanders Interuniversity Institute for Biotechnology (VIB)
2017 Zenith Fellows Award Program
How do specialized support cells in the brain called astroglia impact the onset and progression of Alzheimer’s disease?
Astroglia (also called astrocytes) are the most numerous cell type in the brain. They help support nerve cell function and play an important role in the brain’s immune system. While research suggests that astrocytes are affected in the early stages of Alzheimer’s disease, the majority of data has been collected using Alzheimer’s-like mice. This is a limitation because recent studies have shown that human astrocytes are much more structurally complex and may have different functions than rodent astrocytes. In addition, different variations of the apolipoprotein E (APOE) gene are found in human astrocytes, but not in rodent astrocytes. This is important because a certain variation of this gene, APOE-e4, is associated with increased risk for Alzheimer’s. More research is needed to better understand the unique properties of human astrocytes and the role they may play in Alzheimer’s disease.
Bart DeStrooper, M.D., Ph.D., and colleagues will use stem cell technology to generate human astrocytes and then transplant them into the brain of Alzheimer’s-like mice. To do this, the research team will use a special type of cells, known as induced pluripotent stem cells (iPSCs), which can be obtained non-invasively from human adult skin cells and reprogrammed into astrocytes. This will allow them to study how human astrocytes with different versions of the APOE gene may modulate the disease process in the living brain. The researchers will measure beta-amyloid levels and brain inflammation, and specifically look at how the astrocytes affect nerve cell function in brain regions important for memory.
Results from this study could shed new light on the unique biological functions of APOE in human astrocytes and the role these cells play during Alzheimer’s disease. These findings could also help identify novel targets for drug development aimed at regulating or restoring astrocyte function in the brain to help slow or prevent Alzheimer’s disease.