Homocysteine and methylmalonic acid concentrations in cerebrospinal fluid: relation with age and Alzheimer's disease

J Neurol Neurosurg Psychiatry. 2005 Nov;76(11):1585-7. doi: 10.1136/jnnp.2004.056119.


Background: Homocysteine may be involved in the pathogenesis of late onset Alzheimer's disease. It is implicated in the metabolism of several important pathways in the brain. Methylmalonic acid (MMA) is related to the metabolism of branched chained amino acids and fatty acids.

Objectives: To compare cerebrospinal fluid (CSF) total homocysteine and MMA in elderly subjects, patients with Alzheimer's disease, and younger healthy controls.

Subjects: CSF samples were obtained from 33 patients under 20 years of age; 28 patients aged 21 to 60 years; 22 normal elderly subjects aged over 60; and 38 Alzheimer patients aged over 60.

Results: CSF total homocysteine increased with age (mean (SD): 57 (35) nmol/l in the youngest group v 123 (89) nmol/l in the elderly group (p<0.001)). There was no difference between the elderly group and Alzheimer patients (115 (62) nmol/l). CSF MMA did not differ in the elderly group and the Alzheimer group (38 (13) v 35 (14) ng/ml). In the youngest group, it was significantly higher (60 (15) ng/ml).

Conclusions: CSF total homocysteine is not increased in Alzheimer's disease compared with age matched controls. CSF total homocysteine was correlated with age. The decrease in CSF MMA levels with age eliminates a lack of vitamin B-12 at neuronal level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / physiopathology*
  • Female
  • Homocysteine / cerebrospinal fluid*
  • Humans
  • Male
  • Methylmalonic Acid / cerebrospinal fluid*
  • Middle Aged


  • Homocysteine
  • Methylmalonic Acid