Decreased level of 5-methyltetrahydrofolate: A potential biomarker for pre-symptomatic amyotrophic lateral sclerosis

X. Zhang, S. Chen, L. Li, Q. Wang, W. Le

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Background: Several studies have reported that homocysteine (Hcy) is associated with amyotrophic lateral sclerosis (ALS), a neurodegenerative disease without special biomarkers for early diagnosis. Here, we examined the levels of Hcy, folic acid and its metabolic molecule 5-methyltetrahydrofolate (5-MTHF) in SOD1G93A transgenic mouse model of ALS in an attempt to determine whether the change in those molecules can be used as potential biomarkers for the disease. Methods: According to the disease progression, SOD1G93A transgenic mice were divided into early stage group (30 d); pre-symptom group (60 d); symptom group (90 d) and terminal stage group (120 d). LC-MS/MS was used to measure the level of Hcy, folic acid and 5-MTHF in the plasma, spinal cord and cortex of the ALS transgenic SOD1G93A mice at different disease stages. Nissl staining was used to detect the motor neurons survival in the anterior horn of the spinal cord of the SOD1G93A mice. Results: In this study, we demonstrated that the level of 5-MTHF is significantly decreased in the plasma, spinal cord and cortex at the early stages of pre-symptomatic ALS transgenic SOD1G93A mice while folic acid is decreased at the middle to late stages of the disease. Furthermore, we found that the level of Hcy is markedly elevated after the motor symptoms appeared in the ALS mice. Conclusion: Our study suggests that decreased 5-MTHF level may be a potential biomarker for the early stage of the disease in the ALS mice, which may warrant further validating study of 5-MTHF level in ALS patients.

Original languageEnglish (US)
Pages (from-to)102-105
Number of pages4
JournalJournal of the Neurological Sciences
Issue number1-2
StatePublished - Jun 15 2010


  • 5-Methyltetrahydrofolate
  • Amyotrophic lateral sclerosis
  • Biomarker
  • Homocysteine

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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