Methylation status and neurodegenerative markers in Parkinson disease

Clin Chem. 2009 Oct;55(10):1852-60. doi: 10.1373/clinchem.2009.125021. Epub 2009 Aug 13.


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).

MeSH terms

  • Aged
  • Amyloid beta-Peptides / blood*
  • Amyloid beta-Protein Precursor / blood
  • Biomarkers / blood
  • Blood Platelets / metabolism
  • Cognition Disorders / blood
  • Cognition Disorders / physiopathology
  • Female
  • Folic Acid / blood
  • Homocysteine / blood
  • Humans
  • Male
  • Methylation
  • Middle Aged
  • Nerve Degeneration / blood
  • Parkinson Disease / blood*
  • Parkinson Disease / drug therapy
  • Parkinson Disease / physiopathology
  • Peptide Fragments / blood*
  • S-Adenosylhomocysteine / blood*
  • S-Adenosylmethionine / blood*
  • Substantia Nigra / diagnostic imaging
  • Ultrasonography
  • Vitamin B 6 / blood
  • alpha-Synuclein / blood*


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Biomarkers
  • Peptide Fragments
  • alpha-Synuclein
  • amyloid beta-protein (1-42)
  • Homocysteine
  • S-Adenosylmethionine
  • Vitamin B 6
  • Folic Acid
  • S-Adenosylhomocysteine