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.

Keyword

Aged

Aged

80 and over

Alzheimer Disease

cerebrospinal fluid

physiopathology

Amyloid beta-Protein

analysis

cerebrospinal fluid

Asian Americans

Brain

metabolism

physiopathology

Brain Chemistry

physiology

Cerebrospinal Fluid

metabolism

Chromium

analysis

cerebrospinal fluid

Cohort Studies

Copper

analysis

cerebrospinal fluid

Humans

Iron

analysis

cerebrospinal fluid

Male

Manganese

analysis

cerebrospinal fluid

Peptide Fragments

analysis

cerebrospinal fluid

Zinc

analysis

cerebrospinal fluid

Publication and Content Type

ref (subject category)

art (subject category)