S-adenosylmethionine is decreased in the cerebrospinal fluid of patients with Alzheimer's disease

Neurodegener Dis. 2010;7(6):373-8. doi: 10.1159/000309657. Epub 2010 Jun 3.


Background: Increased plasma homocysteine levels have been described as an independent risk factor for Alzheimer's disease (AD), but the underlying pathophysiology is unclear.

Objective: This single-center, cross-sectional, correlational study analyzed homocysteine metabolism in 60 AD patients and 60 control subjects.

Methods: Fasting plasma levels of vitamin B₁₂, folate and homocysteine as well as cerebrospinal fluid (CSF) levels of folate derivates, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and homocysteine were measured. In addition, the apolipoprotein E (APOE) genotype was determined.

Results: As expected, the APOE4 allele was significantly overrepresented in AD patients compared with controls (p < 0.001). Homocysteine plasma levels in the highest quartile were more frequent in the AD patients than in the controls (p = 0.008). In addition, AD patients had significantly lower CSF levels of the methyl group donor SAM (193 ± 31 vs. 207 ± 37 nmol/l; p = 0.032). Accordingly, the SAM/SAH ratio, which represents the methylation capacity, was significantly lower in the CSF of the AD patients (7.6 ± 2.4 vs. 9.1 ± 2.8; p = 0.003). Further, explorative analysis of all subjects showed that CSF SAM levels were lower in carriers of the APOE4 allele compared with noncarriers (189 ± 30 vs. 207 ± 36 nmol/l; p = 0.010). Of the individuals with CSF SAM levels in the lowest quartile, 63% carried the APOE4 allele compared with 17% of the individuals with CSF SAM levels in the highest quartile (Pearson: χ² = 9.9; p = 0.002; odds ratio 0.126, 95% confidence interval 0.32-0.49).

Conclusion: These data suggest that AD is associated with lower CSF SAM levels and that this is at least partly due to an association of the APOE4 allele with reduced SAM levels in the CSF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / genetics
  • Analysis of Variance
  • Apolipoprotein E4 / genetics
  • Chi-Square Distribution
  • Cross-Sectional Studies
  • Fasting / blood
  • Fasting / cerebrospinal fluid
  • Female
  • Folic Acid / cerebrospinal fluid
  • Homocysteine / blood
  • Humans
  • Linear Models
  • Male
  • Mental Status Schedule
  • Middle Aged
  • S-Adenosylmethionine / blood
  • S-Adenosylmethionine / cerebrospinal fluid*
  • Whites


  • Apolipoprotein E4
  • Homocysteine
  • S-Adenosylmethionine
  • Folic Acid