Elemental iron and copper found in the brains of people with Alzheimer’s disease

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A new study identifies the presence of the elemental metals iron and copper in plaques taken from the brains of people with Alzheimer’s disease (AD).

As strange as it may sound, our spongy biological brain needs metals to function. In fact, any organism that depends on chemical processes called oxidation and reduction will need some form of metal to survive.

In the brain, metals like iron, copper and zinc play an important role in many processes. They usually exist as ions, charged molecules that are used in chemical reactions that fuel biological pathways. While their important role in healthy brains is well established, the balance of metals and metal ions in the brain has become the focus of neurodegeneration researchers who suggest that disruption of biological levels of these elements may contribute to proteinopathies such as AD.

Today, British researchers published an article in Scientists progress which reveals tiny amounts of nonionic elemental metal deposits inside the amyloid plaques. These features of AD are often exploited as therapeutic targets for the disease. Aducanumab, a recently approved monoclonal antibody, is designed to bind to aggregated forms of -amyloid.

This discovery, according to the researchers, led by Neil Telling, a professor at Keele University, is the first recorded evidence of elemental copper in the human brain. In an e-mail to Technological networks, Telling elaborated on what this discovery could mean for the brain: “The metallic forms of iron and copper that we have observed and which are presented in this article have markedly different chemical and magnetic properties than their less reactive oxide forms in the brain. which iron and copper are mainly stored in the human body. Metallic copper and iron surfaces are very unstable and easily react with their surroundings, with the potential to cause damage to brain cells.

The study identified tiny deposits of metallic copper and iron. Credit: Neil Telling and James Everett

Metals are classified as biogenic, meaning they were produced by the body, and were found in trace amounts that were only identifiable using a sophisticated imaging technique called ray microscopy. X Synchrotron Scanning Transmission (STXM).

The researchers discovered the deposits unexpectedly when analyzing the brains of two patients who died of Alzheimer’s disease. STXM allows researchers to see what elements are present in specific areas of brain tissue, down to a resolution of around 20 nanometers – in comparison, a human hair is around 90,000 nanometers wide.

The metals have been found in amyloid plaques in patients’ frontal and temporal lobes, regions that contain structures essential for cognition such as the hippocampus. Interestingly, the iron found in the plates appeared to be magnetic, a finding that was confirmed by X-ray Magnetic Circular Dichroism (XMCD) analysis. This technique involved a magnetic field around the samples, which were then bombarded with polarized light rays. By then looking at the X-ray absorption spectra of the samples, the magnetism of iron could be identified.

What do the metals in the brain mean?

The team noted that these tiny elemental metal deposits were accompanied by ionized metals. The authors suggest that repeated reduction and oxidation reactions, where elements have moved between ionization states, could occur in the plates.

These reactions could be caused by the activity of reactive oxygen species (ROS), molecules that also contribute to neuroinflammation and cell death in Alzheimer’s disease. The authors say elemental metals could contribute to this inflammatory state. The authors propose that strategies targeting these metals could facilitate the diagnosis of Alzheimer’s disease using iron-sensitive imaging and could even help reduce the oxidative stress load in the brain of Alzheimer’s disease.

Before these theories can be confirmed, more evidence will be needed. “The importance of these highly reactive metal forms for neurodegenerative diseases such as Alzheimer’s remains to be seen, but their discovery will help researchers understand the complex biochemistry of the brain, including how these metals might be involved in the processes. morbid. It is also expected to answer ongoing questions regarding how metals chemically interact with proteins such as amyloid proteins from which Alzheimer’s plaques are formed. Related studies are underway exploring the links between the shape of metals in the brain and other neurodegenerative diseases such as Parkinson’s disease. Taking into account biochemical metal-based interactions should help build new hypotheses to elucidate the mechanisms involved in these complex brain diseases, ”explains Telling.

Reference:

Everett, J, lermyte, F, Brooks, J et al. Biogenic metallic elements in the human brain? Sci. Av. 2021; 7. doi: 10.1126 / sciadv.abf6707


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