RAPID INDUCTION OF ALZHEIMER A-BETA AMYLOID FORMATION BY ZINC

被引：1413

作者：

BUSH, AI

PETTINGELL, WH

MULTHAUP, G

PARADIS, MD

VONSATTEL, JP

GUSELLA, JF

BEYREUTHER, K

MASTERS, CL

TANZI, RE

机构：

[1] MASSACHUSETTS GEN HOSP, GENET & AGING LAB, BOSTON, MA 02114 USA

[2] HARVARD UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02114 USA

[3] HARVARD UNIV, SCH MED, DEPT PSYCHIAT, BOSTON, MA 02114 USA

[4] UNIV HEIDELBERG, ZENTRUM MOLEK BIOL HEIDELBERG, HEIDELBERG, GERMANY

[5] HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02114 USA

[6] UNIV MELBOURNE, DEPT PATHOL, PARKVILLE, VIC 3052, AUSTRALIA

[7] MENTAL HLTH RES INST VICTORIA, PARKVILLE, VIC, AUSTRALIA

来源：

SCIENCE | 1994年 / 265卷 / 5177期

关键词：

D O I：

10.1126/science.8073293

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A beta(1-40), a major component of Alzheimer's disease cerebral amyloid, is present in the cerebrospinal fluid and remains relatively soluble at high concentrations (less than or equal to 3.7 mM). Thus, physiological factors which induce A beta amyloid formation could provide clues to the pathogenesis of the disease. It has been shown that human A beta specifically and saturably binds zinc. Here, concentrations of zinc above 300 nM rapidly destabilized human A beta(1-40) solutions, inducing tinctorial amyloid formation. However, rat A beta(1-40) binds zinc less avidly and is immune to these effects, perhaps explaining the scarcity with which these animals form cerebral A beta amyloid. These data suggest a role for cerebral zinc metabolism in the neuropathogenesis of Alzheimer's disease.

引用

页码：1464 / 1467

页数：4

共 39 条

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