This study states that Parkinson’s disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta,1 but also depletion of other neurotransmitters, such as serotonin in the striatum and noradrenaline in the hypothalamus and frontal cortex.2, 3 Cerebrospinal fluid (CSF) represents the most proximal source of molecular biomarkers for these deficiencies.4 Although quantification of CSF protein biomarkers improves early diagnosis in Alzheimer’s disease,5 no analogous protein biomarkers for PD diagnosis exist. Neurotransmitter metabolites represent a potential proxy to PD-specific neurodegeneration and may serve as promising biomarkers of disease severity and its progression.

Several studies investigating dopamine metabolites in PD found consistent signatures, in particular, decreased levels of the main dopamine metabolite homovanillic acid (HVA).6-10 However, their utility for monitoring disease progression has been questioned, mainly because of the results of the DATATOP (deprenyl and tocopherol antioxidative therapy of parkinsonism) study in which repeated CSF measurements of dopamine metabolites by gas chromatography–mass spectrometry yielded variable results. Despite efforts to standardize CSF collection, processing, and measurement,11, 12 potential confounding factors on catecholamine levels remain (eg, diurnal changes, total CSF volume) and may impede the reliable quantification.

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