Alzheimer's Breakthrough: Brain Metals That May Drive Disease Progression Revealed

Alzheimer's disease could be better treated, thanks to a breakthrough discovery of the properties of the metals in the brain involved in the progression of the neurodegenerative condition, by an international research collaboration including the University of Warwick in England.

Joanna Collingwood, PhD, an associate professor at the University of Warwick's School of Engineering and expert in trace metals analysis, high resolution imaging, and neurodegenerative disorders, was part of a research team which characterized iron species associated with the formation of amyloid protein plaques in the human brain—abnormal clusters of proteins in the brain. The formation of these plaques is associated with toxicity which causes cell and tissue death, leading to mental deterioration in Alzheimer's patients.

They found that in brains affected by Alzheimer's, several chemically reduced iron species including a proliferation of a magnetic iron oxide called magnetite—which is not commonly found in the human brain—occur in the amyloid protein plaques. The team had previously shown that these minerals can form when iron and the amyloid protein interact with each other. Thanks to advanced measurement capabilities at synchrotron X-ray facilities in the United Kingdom and United States, the team has now shown detailed evidence that these processes took place in the brains of individuals who had Alzheimer's disease. They also made unique observations about the forms of calcium minerals present in the amyloid plaques.

Understanding the significance of these metals to the progression of Alzheimer's could lead to more effective future therapies which combat the disease at its root.

Collingwood says, "Iron is an essential element in the brain, so it is critical to understand how its management is affected in Alzheimer's disease. The advanced X-ray techniques that we used in this study have delivered a step-change in the level of information that we can obtain about iron chemistry in the amyloid plaques. We are excited to have these new insights into how amyloid plaque formation influences iron chemistry in the human brain, as our findings coincide with efforts by others to treat Alzheimer's disease with iron-modifying drugs."

The team, led by an EPSRC-funded collaboration between University of Warwick and Keele University—and which includes researchers from University of Florida and The University of Texas at San Antonio—made their discovery by extracting amyloid plaque cores from two deceased patients who had a formal diagnosis of Alzheimer's disease.

The researchers scanned the plaque cores using state-of-the-art X-ray microscopy at the Advanced Light Source in Berkeley, California, and at beamline I08 at the Diamond Light Source synchrotron in Oxfordshire, UK, to determine the chemical properties of the minerals within them.

They also analyzed the magnetic state of the iron species in the plaques to confirm the presence of various iron minerals including the magnetic iron oxide magnetite.

The research team propose that interactions between iron and amyloid that produce the chemically reduced iron species, including magnetite, may account for toxicity that contributes to the development and progression of Alzheimer's disease.

The research, "Nanoscale Synchrotron X-ray Speciation of Iron and Calcium Compounds in Amyloid Plaque Cores From Alzheimer's Disease Subjects," was published in Nanoscale.

Source: University of Warwick