Curbing Inflammation at Brain’s Barrier in Alzheimer’s Disease
MentorMark Andermann, PhD Boston Children's Hospital
I aim to understand the role of inflammation at the brain’s blood-cerebrospinal fluid barrier in Alzheimer’s disease and how it negatively affects barrier integrity that protects the brain.
In Aim 1, I will investigate immune cells activities at the choroid plexus, an important barrier between the brain and the rest of the body, in Alzheimer’s mouse models. I will use special stains, a high-powered microscope, and a computer to observe and record the immune cells in live action. I will then compare the mouse findings to human specimens. Aim 2 will determine whether the choroid plexus barrier is leaky in Alzheimer’s mouse models by examining cell-to-cell connections and checking brain fluids for the presence of small molecules that are normally found only in the blood.
The choroid plexus is a critical gateway for immune cells to gain entry to the brain. Regulation at this border may be a new way to control brain inflammation. The choroid plexus is small, deeply located within the brain, and free-floating, making it technically challenging to study and heretofore neglected in brain research. We have innovated live imaging with computational algorithms to study cell movements deep in the brain, and my study will be the first investigation of inflammation at the choroid plexus as a potential treatment target for Alzheimer’s disease. My study will provide conceptual validation of a new research direction, support my future independent research, and raise awareness of choroid plexus inflammation in Alzheimer’s disease and related dementia. Awareness will bring funding opportunities to encourage and support next generation researchers to pursue this topic and eventually lead to discovery of new therapies that target the immune infiltration process across the choroid plexus barrier to ensure optimal levels of immune activation sufficient to eliminate pathogens and damaged cells without causing chronic inflammation.