Alpha-Synuclein as a Biomarker of Parkinson's Disease: Good, but Not Good Enough

Parkinson's disease (PD) is the second most common neurodegenerative disorder of the elderly, presenting primarily with symptoms of motor impairment. The disease is diagnosed most commonly by clinical examination with a great degree of accuracy in specialized centers. However, in some cases, non-classical presentations occur when it may be difficult to distinguish the disease from other types of degenerative or non-degenerative movement disorders with overlapping symptoms. The diagnostic difficulty may also arise in patients at the early stage of PD. Thus, a biomarker could help clinicians circumvent such problems and help them monitor the improvement in disease pathology during anti-parkinsonian drug trials. This review first provides a brief overview of PD, emphasizing, in the process, the important role of alpha-synuclein in the pathogenesis of the disease. Various attempts made by the researchers to develop imaging, genetic, and various biochemical biomarkers for PD are then briefly reviewed to point out the absence of a definitive biomarker for this disorder. In view of the overwhelming importance of alpha-synuclein in the pathogenesis, a detailed analysis is then made of various studies to establish the biomarker potential of this protein in PD; these studies measured total alpha-synuclein, oligomeric, and post-translationally modified forms of alpha-synuclein in cerebrospinal fluid, blood (plasma, serum, erythrocytes, and circulating neuron-specific extracellular vesicles) and saliva in combination with certain other proteins. Multiple studies also examined the accumulation of alpha-synuclein in various forms in PD in the neural elements in the gut, submandibular glands, skin, and the retina. The measurements of the levels of certain forms of alpha-synuclein in some of these body fluids or their components or peripheral tissues hold a significant promise in establishing alpha-synuclein as a definitive biomarker for PD. However, many methodological issues related to detection and quantification of alpha-synuclein have to be resolved, and larger cross-sectional and follow-up studies with controls and patients of PD, parkinsonian disorders, and non-parkinsonian movement disorders are to be undertaken.

Automated summary

Parkinson's disease is the second most common neurodegenerative disorder in the elderly, primarily characterized by motor impairment. The lack of a definitive biomarker for PD has led researchers to focus on the potential role of alpha-synuclein as a key protein in the pathogenesis of the disease. Studies have shown promise in measuring different forms of alpha-synuclein in body fluids and peripheral tissues as a potential biomarker for PD, although methodological issues still need to be addressed through further research.