Clinical Chemistry
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Clinical Chemistry 55: 1852-1860, 2009. First published August 13, 2009; 10.1373/clinchem.2009.125021
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(Clinical Chemistry. 2009;55:1852-1860.)
© 2009 American Association for Clinical Chemistry, Inc.


General Clinical Chemistry

Methylation Status and Neurodegenerative Markers in Parkinson Disease

Rima Obeid1,a, Achim Schadt1, Ulrich Dillmann2, Panagiotis Kostopoulos2, Klaus Fassbender2 and Wolfgang Herrmann1,a

1 Department of Clinical Chemistry and Laboratory Medicine, 2 Department of Neurology, University Hospital of Saarland, Homburg, Germany.

aAddress correspondence to these authors at: University Hospital of Saarland, Department of Clinical Chemistry and Laboratory Medicine, Gebäude 57, D-66421 Homburg/Saar, Germany. Fax 00-49-68411630703; e-mail rima.obeid{at}uniklinikum-saarland.de, kchwher{at}uniklinikum-saarland.de

Background: Increased concentrations of plasma total homocysteine (tHcy) have been associated with age-related diseases, including dementia, stroke, and Parkinson disease (PD). Methylation status might link Hcy metabolism to neurodegenerative proteins in patients with PD.

Methods: We tested blood samples from 87 patients with PD (median age 68 years; 35 men) for tHcy, methylmalonic acid (MMA), vitamin B12, vitamin B6, folate, S-adenosyl methionine (SAM), S-adenosyl homocysteine (SAH), and amyloid-β(1–42). We collected citrate blood from a subset of 45 patients to prepare platelet-rich plasma, and we used washed platelets to prepare cell extracts for amyloid precursor protein (APP) and {alpha}-synuclein assays. We used brain parenchyma sonography to estimate the substantia nigra echogenic area in a subset of 59 patients.

Results: Serum concentrations of tHcy were increased in PD patients (median 14.8 µmol/L). tHcy (β coefficient = –0.276) and serum creatinine (β = –0.422) were significant predictors of the ratio of SAM/SAH in plasma (P < 0.01). The plasma SAM/SAH ratio was a significant determinant for DemTect scores (β = 0.612, P = 0.004). Significant negative correlations were found between concentrations of SAH in plasma and platelet APP and between SAM and platelet {alpha}-synuclein. A larger echogenic area of the substantia nigra was related to higher serum concentrations of MMA (P = 0.016).

Conclusions: Markers of neurodegeneration (APP, {alpha}-synuclein) are related to markers of methylation (SAM, SAH) in patients with PD. Better cognitive function was related to higher methylation potential (SAM/SAH ratio).







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Copyright © 2009 by the American Association for Clinical Chemistry.