- Oxidized iron and copper are vital for the operation of numerous enzymes in the human body.
- Research has implicated disruptions in the regulation of these and other charged metal ions in neurodegenerative disorders, including Alzheimer’s disease.
- Researchers were surprised to discover highly reactive particles of elemental iron and copper in postmortem brain samples from people with Alzheimer’s.
- The metals appeared to be stabilized within the beta-amyloid plaques that are a hallmark of the disease.
- The discovery could provide insights into how the disease progresses and possibly lead to new ways of diagnosing and treating it.
For the first time, scientists have found tiny deposits of elemental, uncharged iron and copper in human tissue.
An international team of researchers discovered the metals in postmortem brain samples from two individuals who had Alzheimer’s disease.
Metal ions, which are metal atoms with a net positive charge after losing one or more electrons, are essential components of many enzymes that catalyze chemical reactions in cells.
These positive ions can strip the electrons from other molecules, oxidizing these molecules.
However, the deposits of copper and iron that the scientists identified in the brain tissue of people with Alzheimer’s were in their elemental, uncharged form.
These are highly reactive metal atoms that, under normal circumstances, would rapidly undergo oxidation to form more chemically stable ions.
Previously, scientists have only identified elemental metals such as these in microorganisms, viruses, and plants.
The researchers found the metals within beta-amyloid plaques, which are the clumps of protein that are a hallmark of Alzheimer’s disease.
Previous research has linked changes in the metabolism of copper and iron in brain tissue to neurodegenerative diseases, including the formation of amyloid plaques in Alzheimer’s disease.
The tiny deposits of elemental iron that the team found in the new study were magnetic, so in principle, doctors could use them for diagnosis or as a marker of disease progression.
The research appears in the journal Science Advances.
Powerful X-rays
The study was a collaboration between scientists from Keele University and the University of Warwick in the United Kingdom and those at the University of Texas at San Antonio in the United States.
The team used exceptionally powerful X-rays from the U.K.’s national synchrotron Diamond Light Source and the Advanced Light Source in California to image the brain tissue.
Synchrotrons accelerate electrons to almost light speed, generating brilliant beams of light that can probe the atomic structure of matter.
The deposits of elemental iron and copper that the scientists identified were on the nanoscale, meaning that they were approximately 10,000 times smaller than a pinhead.
“This is a fascinating and unexpected discovery, enabled by the sensitivity and precision of the synchrotron techniques we have used to study these human-brain-derived samples,” says co-author Joanna Collingwood, Ph.D., who heads the Trace Metals in Medicine Laboratory at the University of Warwick.
“We know that certain living systems can produce elemental forms of metals, so it will be important to discover if these arise from equivalent but previously undiscovered pathways in humans, or if the metallic forms arise as a direct consequence of disease,” she adds.
As elemental metals are so reactive, they can damage nerve tissue, so the brain may lock them up inside the plaques to avoid this.
“It is entirely feasible that beta-amyloid prevents the elemental iron and copper from oxidizing,” said co-author Neil Telling, Ph.D., professor of biomedical nanophysics at Keele University.
“These elemental phases are extremely reactive to oxygen, so for us to be capable of measuring them using X-ray microscopy must mean their oxidation state has been stabilized in some capacity,” he added.
He told Medical News Today that there is some evidence that soluble beta-amyloid may aggregate into insoluble plaques in the brains of people with Alzheimer’s disease to prevent reactive metal atoms from damaging nearby brain cells.
Ruling out contamination
Could the metallic deposits in the brain samples simply be contaminants, perhaps from particulate matter in the air?
Prof. Telling explained that nanoparticles of elemental iron and copper from the environment would oxidize.
He and his colleagues conducted further control tests on such particles and found that they oxidized during sample preparation and examination.
“Indeed, our inability to prevent the oxidation of these metal standards makes our observation of elemental iron and copper in amyloid plaques all the more remarkable,” said Prof. Telling.
Next, he said, the research team plans to look for metallic nanoparticles elsewhere in the brain.
If they are only associated with amyloid plaques, this will help neuroscientists figure out what they are doing there and what role they play in Alzheimer’s disease.
“This line of research could ultimately lead to new treatments that target metals, as well as the amyloid proteins currently under consideration,” said Prof. Telling.
“The existence of tiny magnetic iron particles within plaques could also help with diagnosis and to monitor disease progression, as they could, in principle. be detected by MRI scanners.”
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