Differential effects of lipid-lowering agents on human cholinesterases

被引:33
作者
Darvesh, S
Martin, E
Walsh, R
Rockwood, K
机构
[1] Dalhousie Univ, Dept Med, Div Neurol, Halifax, NS B3H 2E1, Canada
[2] Dalhousie Univ, Dept Med, Halifax, NS B3H 2E1, Canada
[3] Mt St Vincent Univ, Dept Chem, Halifax, NS B3H 2E1, Canada
基金
加拿大健康研究院;
关键词
acetylcholinesterase; Alzheimer's disease; butyrylcholinesterase; dementia; lipid-lowering agents; statins;
D O I
10.1016/j.clinbiochem.2003.09.004
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Objectives: Epidemiologic reports indicate that lipid-lowering agents (LLAs) protect against dementia. We hypothesized that LLAs might affect cholinergic systems. The effects of LLAs on the activity of cholinesterases were examined. Design and methods: Odds ratios and relative risks were calculated from clinical studies of LLAs and dementia and compared with their impacts on human cholinesterases. Representative LLAs were examined for their effects on the activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using Ellman's assay. Results: Epidemiological studies, but not clinical trials, showed lower odds of dementia in patients taking "statins". Comparison of LLAs indicated that "statins" most consistently produced apparent protection. Individual "statins" showed differential cholinesterase inhibition. Lovastatin and simvastatin significantly inhibited butyrylcholinesterase, while mevastatin, pravastatin and the "non-statins" did not. None of the LLAs inhibited acetylcholinesterase. Conclusions: Some "statins" inhibit butyrylcholinesterase. This inhibition suggests a possible means whereby "statins" could protect against dementia. (C) 2003 The Canadian Society of Clinical Chemists. All rights reserved.
引用
收藏
页码:42 / 49
页数:8
相关论文
共 53 条
[21]  
Greig NH, 2001, CURR MED RES OPIN, V17, P159
[22]   Butyrylcholinesterase: An important new target in Alzheimer's disease therapy [J].
Greig, NH ;
Lahiri, DK ;
Sambamurti, K .
INTERNATIONAL PSYCHOGERIATRICS, 2002, 14 :77-91
[23]   Cholinesterase inhibitors for Alzheimer's disease [J].
Grutzendler, J ;
Morris, JC .
DRUGS, 2001, 61 (01) :41-52
[24]   Butyrylcholinesterase in the life cycle of amyloid plaques [J].
Guillozet, AL ;
Smiley, JF ;
Mash, DC ;
Mesulam, MM .
ANNALS OF NEUROLOGY, 1997, 42 (06) :909-918
[25]   The impact of the use of statins on the prevalence of dementia and the progression of cognitive impairment [J].
Hajjar, L ;
Schumpert, J ;
Hirth, V ;
Wieland, D ;
Eleazer, GP .
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2002, 57 (07) :M414-M418
[26]   Is there a connection between the concentration of cholesterol circulating in plasma and the rate of neuritic plaque formation in Alzheimer disease? [J].
Haley, RW .
ARCHIVES OF NEUROLOGY, 2000, 57 (10) :1410-1412
[27]  
HARTZSCHUTT CG, 1991, J HIRNFORSCH, V32, P317
[28]   Structural mechanism for statin inhibition of HMG-CoA reductase [J].
Istvan, ES ;
Deisenhofer, J .
SCIENCE, 2001, 292 (5519) :1160-1164
[29]   Statins and the risk of dementia [J].
Jick, H ;
Zornberg, GL ;
Jick, SS ;
Seshadri, S ;
Drachman, DA .
LANCET, 2000, 356 (9242) :1627-1631
[30]   Mechanism of action of niacin on lipoprotein metabolism [J].
Kamanna V.S. ;
Kashyap M.L. .
Current Atherosclerosis Reports, 2000, 2 (1) :36-46