Nanoscale copper and iron deposits found in amyloid plaque may play a role in Alzheimer disease (AD), according to a recent study published in Science Advances.

Copper, iron, and zinc are found in the human brain in trace amounts and assist with oxidative metabolism. Disruptions in brain metal homeostasis have been tied to the development of neurodegenerative disorders, including AD. Altered copper and iron homeostasis has been linked to amyloid plaque formation, a characteristic of AD.

The researchers in the current study examined the chemical state of iron and copper within amyloid plaque to learn more about the disease. The researchers used synchrotron-based scanning transmission x-ray microscopy (STXM) to determine nanoscale spatial distribution and the chemical state of these 2 metals in amyloid plaque in 2 AD patients.


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The researchers said that this is the first discovery of elemental metallic copper in brain tissue. High-resolution mapping showed nanoscale variation in copper speciation, with both oxidized (Cu2+) and chemically reduced (Cu+/Cu0) phases present.

“The presence of copper in multiple oxidation states within an individual plaque suggests that redox cycling of copper may occur within these structures,” the researchers stated. “A further amyloid plaque core from [1] subject was also found to contain chemically reduced copper.”

The researchers’ observations of copper and iron in human brain tissue, formed within amyloid plaque cores “will stimulate new thinking about the role of metals in human neurobiology and may provide new insights into the etiology of Alzheimer’s and related neurodegenerative diseases,” the researchers stated.

“Biogenic metallic elements, previously observed only in microorganisms, viruses, and plants, can also occur in humans. The reactivity of these metallic phases differs from their metal oxide counterparts previously detected in the human brain and has the scope to redefine our understanding of metal neurochemistry and the role of metal toxicity in neurodegenerative diseases.”

Reference

Everett J, Lermyte F, Brooks J, et al. Biogenic metallic elements in the human brain? Sci Adv. Published online June 9, 2021. doi:10.1126/sciadv.abf6707