Redox-active Cu(II)-Aβ causes substantial changes in axonal integrity in cultured cortical neurons in an oxidative-stress dependent manner.

Abstract

BACKGROUND:

The beta-amyloid (Aβ) peptide comprises the amyloid plaques that characterise Alzheimer's disease (AD), and is thought to significantly contribute towards disease pathogenesis. Oxidative stress is elevated in the AD brain, and there is substantial evidence that the interaction between Aβ and redox-active copper is a major contributing factor towards oxidative stress in AD.

RESULTS:

The major findings of this study are that redox-active Cu(II)-Aβ causes pronounced axonal pathology in long-term neuronal cultures, including axonal fragmentation and the formation of hyperphosphorylated tau-immunoreactive axonal swellings. Notably, MAP-2 expressing dendritic processes remain largely un-affected by Cu(II)-Aβ treatment. These dystrophic axonal manifestations resemble some of the characteristic neuritic pathology of the AD brain. We show that Cu(II)-Aβ directly causes formation of intra-axonal swellings via the generation of free radicals and subsequent efflux of K+ out of neurons.

CONCLUSION:

In summary, we report that redox-active Cu(II)-Aβ can induce substantial neurodegenerative changes in mature neurons, and may have an important role to play in the slowly progressing pathogenesis of AD.

• Authors: Claire Howells, Katrina Saar, Emma Eaton, Shannon Ray, Peep Palumaa, Lana Shabala, Paul A Adlard, William Bennett, Adrian K West, Gilles J Guillemin, Roger S Chung
• Journal: Experimental neurology (Exp Neurol) Vol. 237 Issue 2 Pg. 499-506 (Oct 2012) ISSN: 1090-2430 [Electronic] United States
• PMID: 22691462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Copper

Topics

• Alzheimer Disease (metabolism, pathology)
• Amyloid beta-Peptides (chemistry, metabolism, toxicity)
• Animals
• Axons (drug effects, pathology)
• Blotting, Western
• Cells, Cultured
• Cerebral Cortex (drug effects, pathology)
• Copper (chemistry, metabolism, toxicity)
• Immunohistochemistry
• Neurons (drug effects, pathology)
• Oxidation-Reduction
• Oxidative Stress (physiology)
• Rats
• Rats, Wistar