α-Synuclein in Parkinson disease and other neurodegenerative disorders

With the aging population in the Western hemisphere, neurodegenerative parkinsonism and dementia will become two of the great public health challenges of this century. A major pillar in the effort to treat these conditions will be the shift from symptomatic treatment to disease modifying therapy. This step will absolutely require cheap and reliable biomarkers; patients will need to be diagnosed before irreversible change has occurred. alpha-Synuclein (alpha S) is a recent candidate biomarker for Lewy body neurodegeneration. It is a 140 amino acid protein that forms the pathological substrate in idiopathic Parkinson's disease (IPD), dementia with Lewy bodies (DLB), as well as multiple system atrophy (MSA), a group of disorders collectively known as the synucleopathies. Biomarker research has investigated alpha S in blood, skin and cerebrospinal fluid (CSF). Plasma assays have demonstrated inconsistent results but CSF assays show a higher degree of uniformity, mostly demonstrating lower levels of alpha S in patients with Lewy body disease compared to controls. These results are not yet accurate or reliable enough to use as screening tools or isolated diagnostic tests in established disease. It has become clear that factors other than neurodegeneration affect alpha S concentrations in these tissue samples, such as genetic and environmental influences. Future studies using standardized techniques and larger patient numbers are awaited to realise the full potential of alpha S as a more definitive diagnostic biomarker.