期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 18, 期 4, 页码 819-828出版社
IOS PRESS
DOI: 10.3233/JAD-2009-1187
关键词
Alzheimer's disease; amyloid-beta; cerebrospinal fluid; homocysteine; phosphorylated tau
资金
- German Federal Ministry of Education and Research (BMBF) [01GI0711]
Disturbed homocysteine metabolism is a risk factor for Alzheimer's disease (AD) and may contribute to the disease pathophysiology by increasing both amyloid-beta (A beta) production and phosphorylated tau (P-tau) accumulation. Here, we evaluated the relationship between the cerebrospinal fluid (CSF) concentrations of homocysteine (Hcys), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and 5-methyltetrahydrofolate (5-MTHF), and the markers for AD pathology, A beta(1-42) and P-tau181, in 98 cognitively healthy subjects aged 16-81 years and 54 AD patients. In multivariate regression tests including age, gender, creatinine, and presence of the apolipoprotein E epsilon 4 allele, P-tau181 was associated with SAH (beta = 0.490; p < 0.001), 5-MTHF (beta = -0.273; p = 0.010) levels, and SAM/SAH ratio (beta = -0.319; p = 0.013) in controls, and with SAH (beta = 0.529; p = 0.001) in AD patients. The levels of A beta(1-42) were not associated with the CSF concentrations of Hcys, SAM, SAH, or 5-MTHF neither in the AD nor in the control group. The results suggest that alteration of the homocysteine metabolism is related to increased accumulation of phosphorylated tau and may contribute to the neurofibrillary pathology in normal aging and in AD.
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