Unraveling Pathophysiological Mechanisms of Parkinson's Disease: Contribution of CSF Biomarkers

Abstract

Diagnosis of Parkinson's disease (PD) relies on clinical history and physical examination, but misdiagnosis is common in early stages. Identification of biomarkers for PD may allow for early and more precise diagnosis and provide information about prognosis. Developments in analytical chemistry allow for the detection of a large number of molecules in cerebrospinal fluid (CSF), which are known to be associated with the pathogenesis of PD. Given the pathophysiology of PD, CSF α-synuclein species have the strongest rationale for use, also providing encouraging preliminary results in terms of early diagnosis. In the field of classical Alzheimer's disease (AD) biomarkers, low CSF Aβ₄₂ levels have shown a robust prognostic value in terms of development of cognitive impairment. Other CSF biomarkers including lysosomal enzymes, neurofilament light chain, markers of neuroinflammation and oxidative stress, although promising, have not proved to be reliable for diagnostic and prognostic purposes yet. Overall, the implementation of CSF biomarkers may give a substantial contribution to the optimal use of disease-modifying drugs.

Keywords: Alzheimer’s disease biomarkers; Cerebrospinal fluid biomarkers; Parkinson’s disease; alpha-synuclein; inflammation; lysosomal enzymes; neurofilament light chain; oxidative stress.

Figure 1.

The figure shows the main pathophysiological mechanisms involved in PD and reflected in CSF.