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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-34870

Linnebank, M; Popp, J; Smulders, Y; Smith, D; Semmler, A; Farkas, M; Kulic, L; Cvetanovska, G; Blom, H; Stoffel-Wagner, B; Kölsch, H; Weller, M; Jessen, F (2010). S-Adenosylmethionine is decreased in the cerebrospinal fluid of patients with Alzheimer's disease. Neurodegenerative Diseases, 7(6):373-378.

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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 B(12), 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: chi(2) = 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.


34 citations in Web of Science®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
04 Faculty of Medicine > Psychiatric University Hospital Zurich > Division of Psychiatric Research and Clinic for Psychogeriatric Medicine
Dewey Decimal Classification:610 Medicine & health
Deposited On:15 Jul 2010 14:37
Last Modified:01 Jul 2016 10:53
Additional Information:© 2010 S. Karger AG
Publisher DOI:10.1159/000309657
PubMed ID:20523031

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