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


CONCLUSIONS
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.
Department of Neurology, University Hospital Zurich, Zurich, Switzerland. michael.linnebank@usz.ch
Michael
M
Linnebank
Julius
J
Popp
Yvo
Y
Smulders
Desiree
D
Smith
Alexander
A
Semmler
Melinda
M
Farkas
Luka
L
Kulic
Gabriela
G
Cvetanovska
Henk
H
Blom
Birgit
B
Stoffel-Wagner
Heike
H
Kölsch
Michael
M
Weller
Frank
F
Jessen
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D005215:Fasting / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D005492:Folic Acid / Q000134:cerebrospinal fluid; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016014:Linear Models; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D012436:S-Adenosylmethionine / Q000097:blood / Q000134:cerebrospinal fluid*; D044465:White People
D053327:Apolipoprotein E4; D006710:Homocysteine; D012436:S-Adenosylmethionine; D005492:Folic Acid