Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer's disease transgenic mice

被引：1391

作者：

Cherny, RA

Atwood, CS

Xilinas, ME

Gray, DN

Jones, WD

McLean, CA

Barnham, KJ

Volitakis, I

Fraser, FW

Kim, YS

Huang, XD

Goldstein, LE

Moir, RD

Lim, JT

Beyreuther, K

Zheng, H

Tanzi, RE

Masters, CL

Bush, AI ^{[1
]}

机构：

[1] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia

[2] Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia

[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Oxidat Biol Genet, Charlestown, MA 02129 USA

[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Aging Unit, Charlestown, MA 02129 USA

[5] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA

[6] Univ Gothenburg, Sahlgrenska Univ Sjukhuset, Psychiat Sect, Inst Clin Neurosci, Molndal, Sweden

[7] Biomol Res Inst, Parkville, Vic 3052, Australia

[8] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol & Genet, Charlestown, MA 02129 USA

[9] Heidelberg Univ, ZMBH, D-69120 Heidelberg, Germany

[10] Baylor Coll Med, Huffington Ctr Aging, Dept Mol & Human Genet, Houston, TX 77030 USA

来源：

NEURON | 2001年 / 30卷 / 03期

关键词：

D O I：

10.1016/S0896-6273(01)00317-8

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Inhibition of neocortical beta -amyloid (A beta) accumulation may be essential in an effective therapeutic intervention for Alzheimer's disease (AD). Cu and Zn are enriched in A beta deposits in AD, which are solubilized by Cu/Zn-selective chelators in vitro. Here we report a 49% decrease in brain A beta deposition (-375 mug/g wet weight, p = 0.0001) in a blinded study of APP2576 transgenic mice treated orally for 9 weeks with clioquinol, an antibiotic and bioavailable Cu/Zn chelator. This was accompanied by a modest increase in soluble A beta (1.45% of total cerebral A beta); APP, synaptophysin, and GFAP levels were unaffected. General health and body weight parameters were significantly more stable in the treated animals. These results support targeting the interactions of Cu and Zn with A beta as a novel therapy for the prevention and treatment of AD.

引用

页码：665 / 676

页数：12

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