Although the clinical features of Parkinson's disease (PD) and its changes in the brain are unmistakable, it lacks identified biochemical clues that could enhance early diagnosis of this disorder. We also need measurable substances â€" biomarkers â€" that would enhance our abilities to study the progression of this disease. Such biomarkers could help at diagnosis and would provide insight into possible subtypes of PD. With these research tools, it might be possible gauge the effects of neuroprotective treatments using fewer patients and shorter periods of time than conventional methods now require. It is also likely that biomarkers of PD might also point to mechanisms of causation or other aspects of the disease process. In recent years, several powerful analytical tools have been developed for exploring biochemical changes in disease. Laboratory techniques for separating minute amounts of protein, called 2-dimensional gel electrophoresis (or proteonomic analysis), can provide powerful insights into these building blocks of life. Another research methodology called high performance liquid chromatography, also provides a means for categorizing thousands of small molecular substances that might be altered in disease. Used together, these laboratory techniques offer powerful ways for exploring potential biomarkers of PD. In the research supported by the Michael J. Fox Foundation for Parkinson's Research, we will harness these methods to analyze several hundred specimens of cerebrospinal fluid (CSF) from PD patients. These findings will be compared with studies of specimens from healthy controls. Blood and urine specimens from the same subjects will also be analyzed. Our research plan is to carry out a painstaking search for biomarkers among the many thousands of compounds and protein substances present in these specimens. If detected, we will then proceed to identify promising biomarkers. We will integrate this information into extensive clinical information already known about the PD subjects whose specimens we will be analyzing. This work will be coordinated by Peter LeWitt, MD, who directs PD research at the William Beaumont Hospital Research Institute in Royal Oak, Michigan. Kelvin Lee PhD, whose laboratory in the Department of Chemical Engineering at Cornell University has been a leading center of neurodegeneration biomarker research, will serve as a co-investigator. This project will be carried out in collaboration with biostatisticians at the University of Rochester, who helped in the design and analysis of the DATATOP clinical trial that provided CSF and other specimens for this study. The DATATOP trial (support by the National Institutes of Health from 1987-1992) was carried out by the Parkinson Study Group, a North American consortium of PD investigators and also based at the University of Rochester.