Researchers have discovered small deposits of copper and iron in the brains of two deceased Alzheimer’s patients. Minerals are found in the nuclei of amyloid plaques, unfolded proteins, the accumulation of which is typical of Alzheimer’s disease. Charged iron and copper ions are present in many enzymes and proteins in the brain even in healthy people, however, the discovery of primary metal molecules associated with Alzheimer’s disease is new. It raises the question of how these metallic nanoparticles are formed and what effect they have on neurodegenerative diseases.
Iron and copper ions play an important role in the normal functioning of the brain: many enzymes and proteins contain positively charged metal particles which, through interactions with other substances, participate in the production of messenger substances in the brain, for example. Until now, it was assumed that metals have always existed in a charged form, that is, in the form of ions, such as iron oxide or copper oxide. They can assume different states of charge: the copper ions can be monovalent or divalent (Cu+ and copper2+), divalent or trivalent iron ions (Fe2+ and Fe3+). Balancing different charged ions is important for healthy brain chemistry. Previous studies have already shown that the shift in ratio may be related to the formation of amyloid plaques that are typical of Alzheimer’s disease.
Mineral elements in amyloid plaques
A team led by James Everett of Keele University in Great Britain has now investigated the distribution and chemical state of the minerals in the brains of Alzheimer’s patients. To do this, the researchers analyzed the nuclei of amyloid plaque they had taken from the frontal and temporal lobes of two deceased Alzheimer’s patients. Under an X-ray microscope, the researchers detected various ionized forms of iron and copper within the plaques – and to their surprise, they also discovered nanoparticles of the metal in its elemental form.
“To our knowledge, this is the first evidence of the metallic element copper and iron in human tissue,” the researchers wrote. “This discovery raises fascinating new questions about the production and role of metallic nanoparticles in the brain, for example whether their formation is linked to neuropathological processes.” Diseases arrive.
The mechanisms have not yet been clarified
The important question is how the elementary mineral particles originated. “There are several plausible explanations for this,” the researchers say. One possibility is that the beta-amyloid protein, from which harmful plaques form, is to blame. The iron and copper ions bound to this protein can be directly reduced chemically. “In light of the higher reduction potential of copper-amyloid-beta complexes compared to other biomolecular copper complexes, this is conceivable,” Everett and colleagues explain. In fact, they were able to show that beta-amyloid reduces divalent copper to monovalent. In this regard, the next step, reduction from the monovalent element copper, can also be envisaged. Since monovalent copper is normally stabilized by oxygen, hypoxia in the brain, as often occurs in neurodegenerative diseases, can promote further decline.
Another possibility is that enzymes are responsible for this process. “Many bacteria, fungi, and plants produce primary metallic nanoparticles, including those made of copper and iron,” the researchers stated. “The mechanisms of these synthesis are not fully understood, but they are thought to occur through enzymatic reduction, in some cases along with glucose oxidation.” Similar mechanisms can also be found in the human brain.
Danger or protection?
It remains unclear what role primary metallic nanoparticles play in the brain. Because it is particularly reactive, it can lead to the formation of reactive oxygen species that cause oxidative stress. “This can enhance inflammatory processes in the brain and contribute to the failure of neurons in affected areas of the brain,” the researchers explained. On the other hand, the fact that these particularly reactive mineral particles are trapped in amyloid plaques could be a mechanism to prevent their harmful effects on other brain structures. “The process of formation and breakdown of amyloid plaques in the human brain, both in healthy individuals and those with Alzheimer’s disease, needs further investigation,” the authors wrote.
More knowledge in this area could one day lead to new therapeutic approaches. The researchers speculate that “chemo-reduced copper and iron, associated with amyloid structures, could represent an innovative target for alternative Alzheimer’s therapies aimed at reducing oxidative stress in affected brain regions.” “This discovery has the potential to redefine our understanding of the neurochemistry of metals and the role of metal toxicity in neurodegenerative diseases.”
Source: James Everett (Keele University, Staffordshire, UK) et al., Science Advances, doi: 10.1126/sciadv.abf6707