Metals such as iron, copper and zinc are elevated in the brains of humans with Alzheimer's disease (AD) and those of some animal models of AD. Two recent studies now show that copper accelerates the pathology of AD by promoting the accumulation of the peptide amyloid-β in the brain.

In the first study, Lisa M. Miller and researchers at Stony Brook University, NY, used synchrotron x-ray fluorescence microscopy to image metal ions in the brains of two AD mouse models. They compared the amyloid-β plaques in AD mice that exhibited neurodegeneration with those in AD mice that showed little neurodegeneration. The plaques in mice with neurodegeneration contained ∼25% more copper (Biomedical Spectroscopy and Imaging 2, 129–139; 2013). These data suggest that impaired neuron function may result from an excess of copper in the brains of these mice, possibly indicating that cellular control of copper levels is altered in AD. Miller's group previously found high levels of copper in human AD plaques as well.

In the second study, a group of scientists led by Rashid Deane (University of Rochester Medical Center, NY) gave very small amounts of copper, equivalent to what people would consume in a normal diet, to healthy mice over a 3-month period. The copper made its way into the blood and accumulated in the vessels that carry blood to the brain, especially in the cellular walls of the capillaries (Proc. Natl. Acad. Sci. USA published online 19 August 2013; doi:10.1073/pnas.1302212110). These capillary cells play an important role in preventing the copper from entering the brain. Lipoprotein receptor-related protein 1 (LRP1), which lines the capillaries, binds with amyloid-β, escorting it into the blood vessels and removing it from the brain. Over time, however, the accumulated copper disrupted the function of LRP1 through oxidation. Furthermore, copper in the brains of the mice stimulated neurons to increase their production of amyloid-β and caused it to bind together in larger complexes. Finally, it provoked inflammation of the brain tissue, promoting the breakdown of the blood–brain barrier.

Copper is ubiquitous in the food supply and also can be found in drinking water and nutritional supplements. Although it appears to be one of the main environmental factors implicated in AD, scientists do not suggest copper be avoided altogether, as certain amounts can be beneficial to health. “The key will be striking the right balance between too little and too much copper consumption,” says Deane.