A-synuclein as a peripheral biomarker for Parkinson’s disease
A.W. Michell, L.M. Luheshi, M.G. Spillantini, R.A. Barker
A biomarker able to reflect the pathological changes that occur within the brain of patients with Parkinson’s disease (PD) would find several uses. Potentially it might help diagnose and subdivide this heterogeneous disease, thus helping to select appropriate patients for clinical trials of neuroprotective and neuroregenerative therapies.
There is increasing evidence that α-synuclein plays a central role in the pathogenesis of PD. Point mutations in this protein have been shown to cause autosomal dominant PD 1, and recently a kindred has been described in which triplication of the α-synuclein gene locus led to familial PD 2. In sporadic PD α-synuclein has been shown to be present in Lewy bodies 3. Furthermore, there is evidence of phosphorylation and other post-translational modifications of α-synuclein in human synucleinopathies 4.
We looked at peripheral α-synuclein expression in blood samples of patients with PD versus controls to determine whether it might be a useful biomarker of disease. α-synuclein was found in the platelets of all subjects, but the absolute amounts were extremely variable, and there did not seem to be a correlation between the level of expression and the disease status.
Many patients with PD show abnormal autonomic function, including excess sweating. We looked for α-synuclein in skin biopsies from patients and controls, and found that there was a high level of expression in some patients and controls, but that it was absent in most others.
Platelet and skin levels of α-synuclein are therefore unlikely to be useful diagnostic biomarkers for PD. The present study did not contain sufficient numbers to determine whether the levels of this protein might be able to subdivide PD on the basis of disease severity, duration or other parameters, although an ongoing collaboration looking at plasma may help to answer these questions.
Reference List
1. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 1997;276:2045-7.
2. Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J et al. alpha-Synuclein locus triplication causes Parkinson's disease. Science 2003;302:841.
3. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature 1997;388:839-40.
4. Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg MS et al. alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat.Cell Biol. 2002;4:160-4.
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