Metallomic Mapping of the Aging Brain in Trg2576 Transgenic Mouse Model

The goal of this project is to perform the first high-resolution metallomic brain maps of key biometals (copper, zinc, iron) during normal brain aging and in Alzheimer’s disease in order to develop disease-modifying treatments that target normalization of biometal distribution and metal-protein interactions in the brain.

In this project, Dr. Lee Goldstein’s lab will deploy unique analytical resources at the Boston University Center for Biometals & Metallomics studying zinc and other key brain biometals and show how they play a critical role in normal brain function and, when altered, lead to the development of Alzheimer’s disease. Recent clinical trials strongly support developing drugs targeting brain biometals and metal-protein interactions as a promising therapeutic strategy for this devastating neurodgenerative disease. However, little is known about the role and distribution of key biometals and essential micronutrients (including copper, zinc and iron) in brain aging and Alzheimer’s disease. This information is critical for rational development of disease-modifying treatments that target normalization of biometal distribution and metal- protein interactions in the brain. In this project, Goldstein and his colleagues will deploy unique analytical resources at the Boston University Center for Biometals & Metallomics to perform the first high-resolution metallomic brain maps of key biometals (copper, zinc, iron) during normal brain aging and in Alzheimer’s disease. These studies will be performed in a well-characterized Alzheimer’s disease transgenic mouse model and validated in human brain specimens.