To view an abstract, select an author from the vertical list on the left.
2017 Grants - Inlay
Generation of a Blood-Brain Barrier from Alzheimer's Disease Patient iPSCs
Matt Inlay, Ph.D.
University of California - Irvine
2017 Alzheimer’s Association Research Grant (AARG)
How do changes in the blood-brain barrier contribute to the accumulation of beta-amyloid in Alzheimer’s disease?
A specialized structure called the blood-brain barrier (BBB) helps maintain a healthy brain environment by tightly regulating what goes in and out of the brain from the circulating blood. Dysfunction of the BBB has been associated with the progression of many neurodegenerative diseases, including Alzheimer’s. The BBB is composed of different cell types including endothelial cells, astrocytes and pericytes, which play an important role in clearing harmful debris from the brain. Researchers hypothesize that during Alzheimer’s disease, damage to the BBB may contribute to the accumulation of beta-amyloid protein into “plaques” in the brain, but more research is needed to understand the underlying mechanisms.
Matt Inlay, Ph.D., and colleagues will create a BBB grown in a laboratory dish using a special type of stem cell called “induced pluripotent stem cells” (iPSCs). iPSCs can be made from skin cells of adults and then “reprogrammed” to become other types of cells. The iPSCs contain genetic information specific to the individual they were collected from and can be used by scientists to study cells made directly from people with Alzheimer’s disease. For their studies, Dr. Inlay and team will transform the iPSCs into the different cell types that form the BBB: astrocytes, endothelial cells and pericytes. Growing the three cell types together will create a more accurate model of the BBB that retains its specialized functions including the system for clearing beta-amyloid. They will determine if the BBB made from cells of individuals who carry the Alzheimer’s-risk gene (APOE-ε4) shows impaired ability to transport and remove the build-up of beta-amyloid.
If successful, this study will be the first to develop an all-human model of the blood-brain barrier using iPSCs from people with Alzheimer’s disease. This work could shed new light on the interactions of the different cell types that form the BBB and help determine how genetic variations associated with Alzheimer’s risk affect BBB function.