Cerebrospinal fluid biomarkers in Parkinson disease

Parkinson disease (PD) begins with a long preclinical phase, which represents both a diagnostic challenge and a potential therapeutic opportunity for early intervention. Parnetti and colleagues discuss growing evidence to support the utility of cerebrospinal fluid levels of various proteins, such as α-synuclein, amyloid-β and tau, as accessible biomarkers for PD diagnosis. The authors emphasise the importance of measuring multiple biomarkers in combination to improve diagnostic accuracy. Clinical diagnosis of Parkinson disease (PD) is difficult in early stages of disease, with high risk of misdiagnosis. The long preclinical phase of PD provides the possibility for early therapeutic intervention once disease-modifying therapies have been developed, but lack of biomarkers for early diagnosis and monitoring of disease progression represents a major obstacle to achievement of this goal. Accordingly, research efforts aimed at identification of novel biomarkers have been increasing in the past 5 years. Cerebrospinal fluid (CSF) is an accessible source of brain-derived proteins, which mirror molecular changes that take place in the CNS. In this Review, we discuss evidence from numerous studies that have focused on identification of candidate CSF biomarkers for PD. Notably, molecular pathways related to α-synuclein, tau and β-amyloid peptides have received considerable attention. CSF levels of the protein DJ-1 are also of interest, although further investigation of this candidate marker is required. These studies support the usefulness of a combination of various CSF biomarkers of PD to increase diagnostic accuracy during early phases of the disease, and to differentiate PD from other neurodegenerative disorders.