A group of researchers say they have made a surprising and potentially very important discovery in the brain of two people with Alzheimer’s disease: traces of a certain form of iron and copper deep inside deposits of amyloid plaque, a key marker of the deadly disease. The finding raises several questions about how Alzheimer’s develops, and may one day point to a new way of detecting or treating the underlying dysfunction that causes it.
Iron and copper are elements found in small amounts throughout the body, including in the brain. They can serve many important functions, such as being parts of enzymes that are essential to our healthy functioning. Both can enter different oxidation states when they are part of a compound, meaning they lose or gain electrons. Because some types of these elements can be dangerous to us, triggering chemical reactions that damage cells, the body usually does a good job of regulating the types of iron and copper that must be present in our system at all times.
However, the regulation of these metals does not appear to work as well in the brain of people with Alzheimer’s disease. Those with the disorder develop deposits of improperly folded amyloid beta and tau, which are called plaques and tangles, respectively. And some evidence has suggested that there are toxic forms of iron and copper inside these plaques.
To better understand this possible link, researchers in the UK, Germany and the US collaborated on a new study, published Wednesday in Science Advances. They used a type of X-ray imaging to analyze the specific chemical composition of plaques taken from the brains of two deceased donors with severe Alzheimer’s. They then found elemental and metallic nanoparticles of iron and copper in the nuclei of these plaques, meaning that the elements had no oxidation – no electrons were missing or added.
Although some species of bacteria, fungi and plants are known to produce this kind of metal, this is the first time this type of iron and copper has been documented in human tissues, according to the authors. And it can help explain how plaques damage the brain.
“The metal forms of iron and copper we observed have distinctly different chemical and magnetic properties from their less reactive oxide forms, where iron and copper are predominantly stored in the human body,” senior author Neil Telling, professor of biomedical nanophysics at Keele University in the UK, told Gizmodo in an email. “The surfaces of metallic copper and iron are very unstable and react easily with their surroundings with the potential to cause damage to brain cells.”
Of course, potential discoveries like this must be further investigated and validated by other researchers before they can be accepted as true. While this is a genuine find, there are many unanswered questions. For example, it has not yet been confirmed whether these metals can only be found in the brains of Alzheimer’s patients. In addition, their exact origin remains a mystery, although previous research by Teling’s team and others suggests that amyloid plaques may trigger chemical reactions capable of transforming less reactive forms of these elements into something more dangerous. Some studies have done that as well raised the possibility that amyloid plates may protect us from these toxic metals, Telling noted, so the relationship between all of these factors may be more complicated than we think.
In any case, Telling and his team plan to continue digging further into this. And if this area continues to show promise, it may well lead to new directions for understanding Alzheimer’s and other neurological disorders associated with rogue proteins, such as Parkinson’s disease.
“This line of research could ultimately lead to new treatments targeting metals as well as the amyloid proteins currently under consideration,” he said. “The existence of small magnetic iron particles in plaques could also help with the diagnosis and to monitor disease progression, as they could in principle be detected by MRI scanners.”