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 α-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 α-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, α-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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