Year 2

The goal of this project has been to understand how neurons made from stem cells that are genetically engineered to develop AD in a dish generate abnormal biochemistry that we can measure with simple assays. In the first year of this project we developed new probes for the pathway we are trying to measure. After disappointing results with molecular techniques, this year we used a drug-based screen instead to begin to unravel complex signaling pathways leading to increased p-tau. In the upcoming year, we will use our newly developed CRISPR ApoE lines and robust astrocyte-neuronal culture system to further understand APP, cholesterol and astrocytic factors in the generation of p-tau.