UZH-Logo

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


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.

Abstract

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.

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.

Citations

34 citations in Web of Science®
44 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

67 downloads since deposited on 15 Jul 2010
21 downloads since 12 months
Detailed statistics

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 > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:15 Jul 2010 14:37
Last Modified:16 Aug 2016 10:13
Publisher:Karger
ISSN:1660-2854
Additional Information:© 2010 S. Karger AG
Publisher DOI:10.1159/000309657
PubMed ID:20523031
Permanent URL: http://doi.org/10.5167/uzh-34870

Download

[img]
Preview
Content: Accepted Version
Filetype: PDF
Size: 1MB
View at publisher
[img]
Preview
Content: Published Version
Filetype: PDF
Size: 114kB

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations