Molecular Changes in the Aging Brain Precede Abeta Deposition

The goal of this study is to determine what common changes occur in Alzheimer’s disease and in aging brain, as a result of inflammation and oxidative stress. We will use state-of-the-art fluorescence imaging techniques that are uniquely suited to detect relative changes in protein conformation in intact and/or live cells without disrupting the protein(s) normal physiological environment. Our laboratory pioneered the development of assays that enable us monitoring conformational changes in presenilin in live cells, in brain of mouse models of Alzheimer’s disease, and in human brain samples. We will complement these novel microscopy approaches by traditional biochemical and functional assays to provide fuller picture of the pathological changes occurring in aging neuron.