Cerebrospinal fluid biomarker candidates for parkinsonian disorders

Abstract

The Parkinsonian disorders are a large group of neurodegenerative diseases including idiopathic Parkinson's disease (PD) and atypical Parkinsonian disorders (APD), such as multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies. The etiology of these disorders is not known although it is considered to be a combination of genetic and environmental factors. One of the greatest obstacles for developing efficacious disease-modifying treatment strategies is the lack of biomarkers. Reliable biomarkers are needed for early and accurate diagnosis, to measure disease progression, and response to therapy. In this review several of the most promising cerebrospinal biomarker candidates are discussed. Alpha-synuclein seems to be intimately involved in the pathogenesis of synucleinopathies and its levels can be measured in the cerebrospinal fluid and in plasma. In a similar way, tau protein accumulation seems to be involved in the pathogenesis of tauopathies. Urate, a potent antioxidant, seems to be associated to the risk of developing PD and with its progression. Neurofilament light chain levels are increased in APD compared with PD and healthy controls. The new "omics" techniques are potent tools offering new insights in the patho-etiology of these disorders. Some of the difficulties encountered in developing biomarkers are discussed together with future perspectives.

Keywords: Parkinson disease; Parkinsonian disorders; biomarkers; cerebrospinal fluid; proteomics.

Figure 1

Simplified and non-exhaustive visual representation of two groups of protein accumulation disorders (synucleinopathies and tauopathies), two major groups of symptoms (Parkinsonism and cognitive impairment), and some but not all possible interactions in-between. All of the depicted disorders are Parkinsonian disorders with the exception of Alzheimer’s disease. The figure is not on scale. AD, Alzheimer’s disease; CBD, corticobasal degeneration; DLB, dementia with Lewy bodies; MSA, multiple system atrophy; PD, Parkinson’s disease; PSP, progressive supranuclear palsy. Dashed line, atypical Parkinsonian disorders.