Elevated Levels of Methylmalonate and Homocysteine in Parkinson’s Disease, Progressive Supranuclear Palsy and Amyotrophic Lateral Sclerosis

Abstract

Background/Aims: Increasing evidence suggests that elevated levels of homocysteine (Hcy) and methylmalonate (MMA) may be involved in the pathogenesis of neurodegenerative diseases. Methods: The urine levels of MMA and serum levels of Hcy as well as folic acid and vitamin B₁₂ were measured in patients suffering from the distinct neurodegenerative diseases progressive supranuclear palsy (PSP), amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD), and compared to age- and gender-matched control subjects. Results: We found significantly elevated concentrations of Hcy (PD 15.1, PSP 15.8, ALS 13.9, control 11.2 µmol/l) and MMA (PD 3.7, PSP 3.1, ALS 3.7, control 1.8 mg/g) in all patient groups in comparison with controls. Levels of Hcy and MMA did not differ significantly between the neurodegenerative diseases. Conclusion: Our findings might imply that Hcy and MMA are released as a consequence of neurodegeneration regardless of the underlying cause and serve as surrogate markers of neurodegeneration. Alternatively they might be directly implicated in the pathogenesis of these diseases. Since elevated levels of both Hcy and MMA are neurotoxic, further studies might investigate the effect of vitamin therapy on disease progression.

Contribution of endogenously produced reactive oxygen species to the activation of podocyte NLRP3 inflammasomes in hyperhomocysteinemia

“…There is accumulating evidence indicating that hHcys contributes to the development of a number of degenerative or sclerotic diseases including coronary artery disease, multiple sclerosis, Parkinson’s disease and many complications associated with aging in general, like osteoporosis and cognitive decline [4, 39–43]. Elevated levels of this methionine amino acid intermediate have also been considered to be an independent risk factor for chronic renal disease, promoting glomerular dysfunction and end-stage renal disease.…”

Serum Vitamins and Heavy Metals in Blood and Urine, and the Correlations among Them in Parkinson’s Disease Patients in China

“…Supplementation with cobalamin improves cerebral and cognitive functions in the elderly [10] . Elevated level of homocysteine is thought to be involved in the pathogenesis of neurodegenerative diseases including PD [11] . A negative correlation was observed between homocysteine and vitamin B 12 concentration in diabetic patients.…”

Tracking and predicting disease progression in progressive supranuclear palsy: CSF and blood biomarkers

“…Patients with MSA showed significantly higher levels of serum insulin-like growth factor-1 compared with controls in a study that also included patients with PD and PSP 34. However, one study did reveal significantly elevated levels of both methylmalonate and homocysteine in all patient groups (PD, PSP, Amyotrophic lateral sclerosis) compared with controls 35. The significance of this is unclear but it has been hypothesised that elevated levels of methylmalonate and homocysteine are neurotoxic.…”