Statins:: drugs for Alzheimer's disease?

被引:42
作者
Eckert, GP
Wood, WG
Müller, WE
机构
[1] Goethe Univ Frankfurt, Bioctr Niederursel, Dept Pharmacol, ZAFES, D-60439 Frankfurt, Germany
[2] Univ Minnesota, Sch Med, Dept Pharmacol, Minneapolis, MN 55455 USA
[3] Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Minneapolis, MN USA
关键词
cholesterol; statins; brain; Alzheimer's disease;
D O I
10.1007/s00702-004-0273-1
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Evidences from cell culture experiments and animal studies suggest a strong link between cholesterol and Alzheimer's disease (AD). This relationship is supported by retrospective epidemiological studies demonstrating that statin treatment reduced the prevalence of AD in patients suffering from hypercholesterolaemia. The alternative processing of the amyloid-precursor protein (APP) in the brain of AD patients leads to the production of the neurotoxic amyloid-beta protein (A beta), a causative factor for AD pathology. In vitro, this mechanism is modulated by alterations in cellular cholesterol levels. Moreover, lowering cholesterol in animal experiments reduced the production of A beta in most but not all studies. These findings led to prospective clinical trials of cholesterol-lowering statins in AD patients, even if many studies do not support elevated cholesterol levels in serum and brain as a risk factor for Alzheimer's disease. Most of these studies were negative. Thus, up to date there is insufficient evidence to suggest the use of statins for treatment in patients with AD.
引用
收藏
页码:1057 / 1071
页数:15
相关论文
共 75 条
[21]   The role of cholesterol in the biosynthesis of β-amyloid. [J].
Frears, ER ;
Stephens, DJ ;
Walters, CE ;
Davies, H ;
Austen, BM .
NEUROREPORT, 1999, 10 (08) :1699-1705
[22]  
Friedhoff LT, 2001, INT J NEUROPSYCHOPH, V4, P127, DOI 10.1017/S1461145701002310
[23]   Amyloid β-protein affects cholesterol metabolism in cultured neurons:: Implications for pivotal role of cholesterol in the amyloid cascade [J].
Gong, JS ;
Sawamura, N ;
Zou, K ;
Sakai, J ;
Yanagisawa, K ;
Michikawa, M .
JOURNAL OF NEUROSCIENCE RESEARCH, 2002, 70 (03) :438-446
[24]   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
[25]   Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors [J].
Hamelin, BA ;
Turgeon, J .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1998, 19 (01) :26-37
[26]   Medicine - The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics [J].
Hardy, J ;
Selkoe, DJ .
SCIENCE, 2002, 297 (5580) :353-356
[27]   Plasma levels of β-amyloid(1-40), β-amyloid(1-42), and total β-amyloid remain unaffected in adult patients with hypercholesterolemia after treatment with statins [J].
Höglund, K ;
Wiklund, O ;
Vanderstichele, H ;
Eikenberg, O ;
Vanmechelen, E ;
Blennow, K .
ARCHIVES OF NEUROLOGY, 2004, 61 (03) :333-337
[28]   Modulation of secreted β-amyloid precursor protein and amyloid β peptide in brain by cholesterol [J].
Howland, DS ;
Trusko, SP ;
Savage, MJ ;
Reaume, AG ;
Lang, DM ;
Hirsch, JD ;
Maeda, N ;
Siman, R ;
Greenberg, BD ;
Scott, RM ;
Flood, DG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (26) :16576-16582
[29]   Cholesterol distribution in the Golgi complex of DITNC1 astrocytes is differentially altered by fresh and aged amyloid β-peptide-(1-42) [J].
Igbavboa, U ;
Pidcock, JM ;
Johnson, LNA ;
Malo, TM ;
Studniski, AE ;
Yu, S ;
Sun, GY ;
Wood, WG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (19) :17150-17157
[30]   Statins and the risk of dementia [J].
Jick, H ;
Zornberg, GL ;
Jick, SS ;
Seshadri, S ;
Drachman, DA .
LANCET, 2000, 356 (9242) :1627-1631