Zinc and copper modulate Alzheimer Aβ levels in human cerebrospinal fluid

NEUROBIOLOGY OF AGING

卷:30

Article

Strozyk, Dorothea^1,2  Launer, Lenore J.¹  Adlard, Paul A.³  Cherny, Robert A.³  Tsatsanis, Andrew³  Volitakis, Irene³  Blennow, Kai⁴  Petrovitch, Helen⁵  White, Lon R.⁵  Bush, Ashley I.^3,6 

[1] NIA, Lab Epidemiol Demog & Biometry, Neuroepidemiol Sect, NIH, Bethesda, MD 20892 USA

[2] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA

[3] Univ Melbourne, Dept Pathol, Mental Hlth Res Inst Victoria, Melbourne, Vic 3010, Australia

[4] Sahlgrens Univ Hosp, Dept Clin Neurosci, Molndal, Sweden

[5] Kuakini Med Ctr, Pacific Hlth Res Inst, Honolulu, HI USA

[6] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA

关键词: Amyloid;    Alzheimer's disease;    Metalloproteinase;    Cerebrospinal fluid;    Zinc;    Copper;    Iron;    Manganese;    Chromium;   

DOI  :  10.1016/j.neurobiolaging.2007.10.012

来源: Elsevier

【 摘 要 】

Abnormal interaction of beta-amyloid 42 (A beta 42) with copper, zinc and iron induce peptide aggregation and oxidation in Alzheimer's disease (AD). However, in health, A beta degradation is mediated by extracellular metalloproteinases, neprilysin, insulin degrading enzyme (IDE) and matrix metalloproteinases. We investigated the relationship between levels of A beta and biological metals in CSF. We assayed CSF copper, zinc, other metals and A beta 42 in ventricular autopsy samples of Japanese American men (N=131) from the population-based Honolulu Asia Aging Study. There was a significant inverse correlation of CSF A beta 42 with copper, zinc, iron, manganese and chromium. The association was particularly strong in the subgroup with high levels of both zinc and copper. Selenium and aluminum levels were not associated to CSF A beta 42. In vitro, the degradation of synthetic A beta substrate added to CSF was markedly accelerated by low levels (2 mu M) of exogenous zinc and copper. While excessive interaction with copper and zinc may induce neocortical A beta precipitation in AD, soluble A beta degradation is normally promoted by physiological copper and zinc concentrations. (C) 2007 Elsevier Inc. All rights reserved.

【 授权许可】

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