Parkinson disease:progress towards a molecular biomarker for Parkinson disease

Foulds, Penny and Mann, David M A and Mitchell, J Douglas and Allsop, David (2010) Parkinson disease:progress towards a molecular biomarker for Parkinson disease. Nature Reviews Neurology, 6 (7). pp. 359-361. ISSN 1759-4766

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Proteins linked to neurodegenerative diseases can potentially be used as biomarkers. A study now shows that after accounting for confounding variables such as age and blood contamination, cerebrospinal fluid levels of α-synuclein and DJ1 are substantially reduced in patients with Parkinson disease compared with healthy controls or individuals with Alzheimer disease. Parkinson disease (PD) is characterized pathologically by the selective loss of dopaminergic neurons from the substantia nigra, and by the presence of Lewy bodies in surviving cells and Lewy neurites in brain parenchyma (Figure 1). The main protein component of Lewy bodies and Lewy neurites is α-synuclein, which accumulates in a phosphorylated and aggregated form.1 Rare cases of familial PD are caused by missense mutations in the SNCA gene, which encodes α-synuclein. Moreover, duplication and triplication of this gene give rise to late-onset and early-onset familial PD, respectively, indicating that the expression level of α-synuclein might be an important determinant of disease onset and severity.2 Evidence now suggests that α-synuclein is released from cells and is present in cerebrospinal fluid (CSF) and blood plasma.3 These findings have led to increasing interest in this protein and other molecules linked mechanistically to the pathogenesis of PD as potential biomarkers for the diagnosis and/or progression of this disorder and related diseases. One such additional molecule is DJ1, as loss-of-function mutations in PARK7, which encodes DJ1, can cause early-onset PD.2 Hong and colleagues have now carried out an extensive study of both α-synuclein and DJ1 as potential CSF biomarkers for PD.

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Nature Reviews Neurology
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21 Jul 2011 14:25
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21 Sep 2023 01:07