Our goal of characterizing potential Alzheimer therapeutics is based on our success in identifying compounds from the original screening of drugs previously approved by the U.S. Food and Drug Administration for the treatment of other diseases. We will study the changes in pathological proteins that are affected by candidate Alzheimer’s therapeutics in cultured cells, and establish new methods to measure these proteins in blood samples. The significance of this project is illustrated by our progress in exploring candidate proteins as biomarkers potentially acceptable for efficacy readout in future human clinical trials.
This project is a part of the three-dimensional cell culture consortium (3DDS) supported by Cure Alzheimer’s Fund for the purpose of drug screening. The next two years of the project will focus on refining the Alzheimer’s in a Dish model while using it to assess the impact of genetic variants in microglial-associated genes. This research will test newly identified molecules, including those from a library of natural compounds, to understand whether they can be optimized to reverse disease progression. Finally, this project will assess the potential of specific inhibitors of microglial activity in ameliorating Alzheimer’s disease, with a focus on expanding the Alzheimer’s in a Dish model to include more of the cell types and structures implicated in Alzheimer’s disease. Of note, materials from both female and male patients with Alzheimer’s disease will be used in order to provide a more complete picture of the disease.