The study presents a quantitative biomarker of DOPA decarboxylase (DDC) in cerebrospinal fluid (CSF) for the diagnosis of Lewy body disorders such as Lewy body dementia and Parkinson's disease. Using two newly developed immunoassays tested in three clinical cohorts, CSF DDC levels were shown to accurately distinguish patients with Lewy body disease (LBD) from Alzheimer's disease and healthy controls with an area under the curve (AUC) of 0.89 (P~FDR~ = 2.6 × 10^-13). These levels are associated with worse cognitive performance (P < 0.05). DDC detects preclinical stages of LBD in clinically asymptomatic individuals with a positive seed amplification test for α-synuclein (AUC = 0.81, P = 1.0 × 10^-5). The biomarker predicts progression to clinical LBD over 3 years with a hazard ratio of 3.7 per standard deviation (confidence interval 1.1–12.7). DDC levels are also elevated in atypical parkinsonian disorders, but not in other neurodegenerative diseases outside of parkinsonism. The results were replicated in an independent cohort where plasma DDC identified LBD and atypical disorders (AUC = 0.92, P = 1.3 × 10^-14).[1]