Contribution of Neuroinflammation to Alzheimer's Disease
This proposed research is focused on understanding how neuroinflammation influences Alzheimer’s disease progression, particularly, it will define the regulatory role of CHI3L1, a disease biomarker. In aim 1, I will use patient-derived stem cells with Alzheimer's disease predisposing (APOE4) or not predisposing mutations (APOE3). I will generate different brain cell types and induce neuroinflammatory conditions to determine the role of the biomarker and inflammatory molecule, CHI3L1. In aim 2 I will use brain tissues obtained from mouse models of Alzheimer's disease and from Alzheimer's disease patients to provide a cross-platform validation of the findings from aim 1.
Firstly, this proposal is hallmarked by the conceptual advance to study CHI3L1, a long deemed biomarker of unknown function as a potential disease mediator and modifier. Secondly, I will employ the technological breakthrough of using patient-derived stem cells to generate different brain cell types to model the novel aspects of neuroinflammation. Finally, the overall research strategy departs from a neuron-centric convention for AD research and, will provide a new translational research horizon to be explored. The completion of my studies will greatly advance our knowledge on the contribution of neuroinflammation to Alzheimer’s disease pathogenesis and provide potential targets for the development of therapeutics.