Prenatal Disruption of Blood-placenta/Brain Barrier Formation Programs AD Risk Later In Life
Using cutting-edge live imaging techniques in a mouse model, the goal of this project is to uncover the cellular and molecular mechanisms by which inflammation disrupts blood-brain barrier formation and function during and after pregnancy, leading to Alzheimer’s disease-like phenotypes in the adult offspring.
Our rigorous approach monitors prenatal inflammation effects on blood-barriers formation and function longitudinally, from the fetal to the postnatal and adult stages of offspring life. These techniques will be combined with behavioral measures and post-mortem histochemical quantification, throughout the lifespan, of specific molecular markers of blood-barriers establishment and function and of Alzheimer’s disease-related neuropathology. Furthermore, the influence of “gene by environment interactions” will be investigated by testing the impact of prenatal inflammation on the severity of phenotypes in well-characterized transgenic mouse models of Alzheimer’s disease.
This project explores vastly understudied mechanisms and factors contributing to Alzheimer’s disease etiology and will provide invaluable insights into the developmental origins of this devastating disease. The potential discovery of new cellular and molecular pathways, where genes and environment interact and either trigger or increase AD risks, could uncover new therapeutics targets by which disease progression could be slowed down or even prevented all together. Given the very basic science nature of our proposal, potential therapeutic benefits may not be immediate; however, we hope the discoveries brought by this project will lead to identifying new risks for AD etiology, and preventative early interventions in future human generations.