Preclinical biomarkers of Parkinson disease.

The search for markers of preclinical Parkinson disease (PD) is becoming increasingly important because pathogenesis-targeted neuroprotective strategies are being developed for future use in at-risk populations, even before clinical onset of disease. Advances in clinical recognition of early symptoms and signs, development of new neuroimaging probes and technologies, identification of new neuropathological markers of PD, and breakthroughs in genetics and basic neuroscience are gradually translating into better understanding of predisposing and preclinical factors that lead to progressive neurodegeneration. Coupled with system biology tools, progress is being made in the identification of new genomic, transcriptomic, proteomic, lipidomic, and metabolomic molecules and new signaling pathways that are relevant to the pathogenesis of neurodegeneration in PD. These new tools will be critical not only in the discovery of sensitive, specific, and reliable biomarkers of preclinical PD but also in the development of tests that will aid in the early detection and differential diagnosis of parkinsonian disorders and in monitoring disease progression.