The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer's disease

被引:148
作者
Selley, ML [1 ]
Close, DR
Stern, SE
机构
[1] Angiogen Pharmaceut Pty Ltd, College Pk, MD 20740 USA
[2] Australian Natl Univ, Sch Finance & Appl Stat, Canberra, ACT 0200, Australia
[3] Australian Natl Univ, Canberra Hosp, Div Mol Med, John Curtin Sch Med Res, Garran, ACT 2605, Australia
关键词
Alzheimer's disease; homocysteine; vitamin B-12; (E)-4-hydroxy-2-nonenal; plasma; cerebrospinal fluid; lipid peroxidation;
D O I
10.1016/S0197-4580(01)00327-X
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
There is evidence that increased blood concentrations of homocysteine may be a risk factor for Alzheimer's disease. (E)-4-hydroxy-2-nonenal (HNE) is a neurotoxic product of lipid peroxidation that is increased in the ventricular fluid and brains of patients with Alzheimer's disease. We measured the concentrations of homocysteine, HNE, vitamin B-12 and folate in the plasma of 27 patients with Alzheimer's disease and 25 control subjects. There was a statistically significant increase in the plasma concentration of homocysteine (P < 0.001) and HNE (P < 0.001) in the Alzheimer's disease patients compared to the control group, There was a significant decrease in the plasma concentration of vitamin B-12 (P < 0.001) and folate (P = 0.002) in the Alzheimer's group compared to the controls. There was a significant positive correlation between the plasma concentrations of homocysteine and HNE in the patients with Alzheimer's disease (r = 0.661, P < 0.001). A significant negative correlation was found between the plasma concentration of homocysteine and the plasma concentrations of vitamin 13, (r = -0.605, P = 0.0006) and folate (r = 0.586, P = 0.001). We also measured the concentrations of homocysteine, HNE, vitamin 13, and folate in the cerebrospinal fluid (CSF) of 8 patients with Alzhiemer's disease compared to 6 control subjects. The concentrations of homocysteine (P = 0.032) and HNE (P = 0.001) were significantly higher in the CSF of Alzheimer's patients than in the control subjects. There A ere significant positive correlations between the CSF concentrations of homocysteine and HNE (r = 0.924, P = 0.001). There was also a significant positive correlation between the plasma concentration of homocysteine and the CSF concentrations of homocysteine (r = 0.850, P = 0.007) and HNE (r = 0.092. P = 0.002). These results demonstrate that there is a relationship between increased homocysteine concentrations and increased HNE concentrations in Alzheimer's disease. (C) 2002 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:383 / 388
页数:6
相关论文
共 51 条
[1]   Histochemical detection of 4-hydroxynonenal protein in Alzheimer amyloid [J].
Ando, Y ;
Brännström, T ;
Uchida, K ;
Nyhlin, N ;
Näsman, B ;
Suhr, O ;
Yamashita, T ;
Olsson, T ;
El Salhy, M ;
Uchino, M ;
Ando, M .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1998, 156 (02) :172-176
[2]  
Blanc EM, 1997, J NEUROCHEM, V69, P570
[3]  
Blanc EM, 1998, GLIA, V22, P149, DOI 10.1002/(SICI)1098-1136(199802)22:2<149::AID-GLIA6>3.0.CO
[4]  
2-2
[5]  
BONILLA E, 1999, BIOCHIM BIOPHYS ACTA, V141, P171
[6]   4-hydroxynonenal, a product of lipid peroxidation, damages cholinergic neurons and impairs visuospatial memory in rats [J].
Bruce-Keller, AJ ;
Li, YJ ;
Lovell, MA ;
Kraemer, PJ ;
Gary, DS ;
Brown, RR ;
Markesbery, WR ;
Mattson, MP .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1998, 57 (03) :257-267
[7]   Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease [J].
Clarke, R ;
Smith, AD ;
Jobst, KA ;
Refsum, H ;
Sutton, L ;
Ueland, PM .
ARCHIVES OF NEUROLOGY, 1998, 55 (11) :1449-1455
[8]   Acute methionine load-induced hyperhomocysteinemia enhances platelet aggregation thromboxane biosynthesis, and macrophage-derived tissue factor activity in rats [J].
Durand, P ;
LussierCacan, S ;
Blache, D .
FASEB JOURNAL, 1997, 11 (13) :1157-1168
[9]   CHEMISTRY AND BIOCHEMISTRY OF 4-HYDROXYNONENAL, MALONALDEHYDE AND RELATED ALDEHYDES [J].
ESTERBAUER, H ;
SCHAUR, RJ ;
ZOLLNER, H .
FREE RADICAL BIOLOGY AND MEDICINE, 1991, 11 (01) :81-128
[10]   MINI-MENTAL STATE - PRACTICAL METHOD FOR GRADING COGNITIVE STATE OF PATIENTS FOR CLINICIAN [J].
FOLSTEIN, MF ;
FOLSTEIN, SE ;
MCHUGH, PR .
JOURNAL OF PSYCHIATRIC RESEARCH, 1975, 12 (03) :189-198