Discovery, validation and optimization of cerebrospinal fluid biomarkers for use in Parkinson’s disease

ABSTRACT Introduction: Parkinson’s disease (PD) is a complex and phenotypically heterogeneous neurodegenerative disease, for which the diagnosis is mainly based on clinical parameters (even if neuroimaging plays a role in diagnostic assessment); as a consequence, misdiagnosis is common, especially in early stages. Thus, there is an urgent need of having available biomarkers in order to achieve an early and accurate diagnosis. Since molecular changes in the brain are reliably and timely reflected in cerebrospinal fluid (CSF), CSF represents an ideal source for biomarkers of different pathophysiological processes characterizing the disease since its early phases. Areas covered: The aim of this review is to provide an update on the role, development and validation of most studied CSF biomarkers showing a role in the diagnosis and/or prognosis of PD. Oligomeric alpha-synuclein, DJ-1, lysosomal enzymes (namely, glucocerebrosidase) show consistent evidence as potential diagnostic biomarkers of PD. Neurofilament light chain may also have a significant role in differentiating PD from other parkinsonisms. Amyloid beta peptide 1–42 has consistently shown a prognostic value in terms of development of cognitive impairment and dementia in PD patients. Expert commentary: CSF biomarkers represent a very promising approach to early and differential diagnosis of PD. The biomarkers available so far need preanalytical and analytical validation in order to have these CSF biomarkers ready for clinical use.

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