Abstract
Progress in developing disease-modifying therapies in Parkinson’s disease (PD) can only be achieved through reliable objective markers that help to identify subjects at risk. This includes an early and accurate diagnosis as well as continuous monitoring of disease progression and therapy response. Although PD diagnosis still relies mainly on clinical features, encouragingly, advances in biomarker discovery have been made. The cerebrospinal fluid (CSF) is a biofluid of particular interest to study biomarkers since it is closest to the brain structures and therefore could serve as an ideal source to reflect ongoing pathologic processes. According to the key pathophysiological mechanisms, the CSF status of α-synuclein species, markers of amyloid and tau pathology, neurofilament light chain, lysosomal enzymes and markers of neuroinflammation provide promising preliminary results as candidate biomarkers. Untargeted approaches in the field of metabolomics provide insights into novel and interconnected biological pathways. Markers based on genetic forms of PD can contribute to identifying subgroups suitable for gene-targeted treatment strategies that might also be transferable to sporadic PD. Further validation analyses in large PD cohort studies will identify the CSF biomarker or biomarker combinations with the best value for clinical and research purposes.
Highlights
As one of the most common neurodegenerative disorders, Parkinson’s disease (PD)is the fastest growing neurological disorder with regard to age-standardized rates of prevalence, disability and deaths [1]
The research of Cerebrospinal fluid (CSF) biomarkers has deepened our understanding of the biological and molecular processes occurring in the brain
CSF Aβ42 has proved its prognostic use for cognitive impairment in PD
Summary
Is the fastest growing neurological disorder with regard to age-standardized rates of prevalence, disability and deaths [1]. The current PD diagnostic criteria mainly rely on the core motor symptoms—bradykinesia, rigidity and rest tremor Even though these criteria are correctly applied, the rate of misdiagnosis is still up to 20% due to clinical overlap with parkinsonism of other etiologies [2]. Objective and reliable biomarkers are urgently needed, firstly, that identify PD in pre-motor stages and indicate susceptibility 2toofthe. Biomarkers should support the clinical diagnosis and define disease subtype and severity. Biomarkers should reliably track disease progression and serve as pre-motor meaningful endpoints for clinical trials tototestify the impact on disease modification of stages and indicate susceptibility the disease. Represents theserve preferred source endpoints for biomarker discovery trials to testify the impact on disease modification of an intervention.
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