Zinc and copper modulate Alzheimer Abeta levels in human cerebrospinal fluid.
Abnormal interaction of beta-amyloid 42 (Abeta42) with copper, zinc and iron induce peptide aggregation and oxidation in Alzheimer's disease (AD). However, in health, Abeta degradation is mediated by extracellular metalloproteinases, neprilysin, insulin degrading enzyme (IDE) and matrix metalloproteinases. We investigated the relationship between levels of Abeta and biological metals in CSF. We assayed CSF copper, zinc, other metals and Abeta42 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 Abeta42 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 Abeta42. In vitro, the degradation of synthetic Abeta substrate added to CSF was markedly accelerated by low levels (2microM) of exogenous zinc and copper. While excessive interaction with copper and zinc may induce neocortical Abeta precipitation in AD, soluble Abeta degradation is normally promoted by physiological copper and zinc concentrations.
Strozyk
Dorothea
D
Albert Einstein College of Medicine, Department of Neurology, Bronx, NY, USA.
Launer
Lenore J
LJ
Adlard
Paul A
PA
Cherny
Robert A
RA
Tsatsanis
Andrew
A
Volitakis
Irene
I
Blennow
Kaj
K
Petrovitch
Helen
H
White
Lon R
LR
Bush
Ashley I
AI
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000134:cerebrospinal fluid*; D001213:Asian; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000502:physiology; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D002857:Chromium / Q000032:analysis / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D003300:Copper / Q000032:analysis / Q000134:cerebrospinal fluid*; D006801:Humans; D007501:Iron / Q000032:analysis / Q000134:cerebrospinal fluid; D008297:Male; D008345:Manganese / Q000032:analysis / Q000134:cerebrospinal fluid; D010446:Peptide Fragments / Q000032:analysis / Q000134:cerebrospinal fluid; D015032:Zinc / Q000032:analysis / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D002857:Chromium; D008345:Manganese; D003300:Copper; D007501:Iron; D015032:Zinc