Methods for detecting toxic α-synuclein species as a biomarker for Parkinson’s disease

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder and is characterized by the accumulation of α-synuclein (α-syn) into insoluble aggregates known as Lewy bodies and Lewy neurites in the brain. However, prior to the formation of these large aggregates, α-syn forms oligomers and small fibrils, which are believed to be the pathogenic species leading to the death of neurons in the substantia nigra in disease. The majority of aggregated α-syn is phosphorylated, and it is thought that this post-translational modification may be critical in disease pathogenesis. Thus, early detection of the toxic forms of α-syn may provide a window of opportunity for an intervention to halt or slow the progression of neurodegeneration in PD. Expression of α-syn is not restricted to the central nervous system and the protein can be found elsewhere, including bodily fluids and peripheral tissues. This review will examine current methods for detecting toxic forms of α-syn in accessible biospecimens and outline emerging techniques that may provide reliable identification of biomarkers for PD.