Work

Substoichiometric Levels of Cu2+ Ions Accelerate the Kinetics of Fiber Formation and Promote Cell Toxicity of Amyloid-β from Alzheimer Disease

Year: 2010

Type: article

Abstract: A role for Cu(2+) ions in Alzheimer disease is often disputed, as it is believed that Cu(2+) ions only promote nontoxic amorphous aggregates of amyloid-β (Aβ). In contrast with currently held opinion, we show that the presence of substoichiometric levels of Cu(2+) ions in fact doubles the rate of production of amyloid fibers, accelerating both the nucleation and elongation of fiber formation. We suggest that binding of Cu(2+) ions at a physiological pH causes Aβ to approach its isoelectric point, thus inducing self-association and fiber formation. We further show that Cu(2+) ions bound to Aβ are consistently more toxic to neuronal cells than Aβ in the absence of Cu(2+) ions, whereas Cu(2+) ions in the absence of Aβ are not cytotoxic. The degree of Cu-Aβ cytotoxicity correlates with the levels of Cu(2+) ions that accelerate fiber formation. We note the effect appears to be specific for Cu(2+) ions as Zn(2+) ions inhibit the formation of fibers. An active role for Cu(2+) ions in accelerating fiber formation and promoting cell death suggests impaired copper homeostasis may be a risk factor in Alzheimer disease.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m110.171355

Authors: Claire J. Sarell, Shane R. Wilkinson, John H. Viles

Institution: Queen Mary University of London

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430