Methylation status and neurodegenerative markers in Parkinson disease.
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 B(12), vitamin B(6), folate, S-adenosyl methionine (SAM), S-adenosyl homocysteine (SAH), and amyloid-beta(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 micromol/L). tHcy (beta coefficient = -0.276) and serum creatinine (beta = -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 (beta = 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).
Obeid
Rima
R
Department of Clinical Chemistry and Laboratory Medicine, Department of Neurology, University Hospital of Saarland, Homburg, Germany. rima.obeid@uniklinikum-saarland.de
Schadt
Achim
A
Dillmann
Ulrich
U
Kostopoulos
Panagiotis
P
Fassbender
Klaus
K
Herrmann
Wolfgang
W
D000368:Aged; D016229:Amyloid beta-Peptides / Q000097:blood*; D016564:Amyloid beta-Protein Precursor / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism; D003072:Cognition Disorders / Q000097:blood / Q000503:physiopathology; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009410:Nerve Degeneration / Q000097:blood; D010300:Parkinson Disease / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D010446:Peptide Fragments / Q000097:blood*; D012435:S-Adenosylhomocysteine / Q000097:blood*; D012436:S-Adenosylmethionine / Q000097:blood*; D013378:Substantia Nigra / Q000000981:diagnostic imaging; D014463:Ultrasonography; D025101:Vitamin B 6 / Q000097:blood; D051844:alpha-Synuclein / Q000097:blood*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D010446:Peptide Fragments; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42); D006710:Homocysteine; D012436:S-Adenosylmethionine; D025101:Vitamin B 6; D005492:Folic Acid; D012435:S-Adenosylhomocysteine