This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human neurodegenerative diseases, such as Alzheimer's disease, affect more than 20 million people worldwide and represent the fourth leading cause of death and a major cause of disability amongst adults in Western societies. This novel partnership of investigators brings together the biomedical, basic and structural sciences. Our team is uniquely positioned to harness the power of the Canadian Light Source synchrotron and Stanford Synchrotron Radiation Laboratories to the genetic power of Drosophila to identify chemical and cellular changes occurring during neurodegeneration. Only very small animals can be visualized using our techniques. The fruitfly is ideal because brain pathology seen in Alzheimer's disease and Parkinson's disease can be reproduced in the fly. Furthermore, flies respond to drugs used to treat Parkinson's disease. Using established fly models of neurodegeneration, we will identify and quantify iron, zinc, manganese and copper in the brain and if they accumulate we will localize them to specific brain regions using x-ray absorption spectroscopy imaging. The synchrotron also enables us to determine if unusual or toxic chemical forms of these metals are associated with neurodegeneration. We will also investigate how metals accumulate over time and how this along with their location in the brain relates to disease progression and cellular pathology. Finally we will determine which therapeutic drugs can reduce or prevent the accumulation of toxic metals in the brain. This work will translate into new assay systems for drug efficacy testing and may lead to better early diagnosis by identifying which metals and which chemical forms of a metal appear early in Alzheimer's and Parkinson's disease.