Metallic drivers of Alzheimer’s disease

The detection of iron and calcium compounds in amyloid plaque cores

X-ray spectromicroscopy at the Scanning X-ray Microscopy beamline (I08), here at Diamond, has been utilised to pinpoint chemically reduced iron and calcium compounds within protein plaques derived from brains of Alzheimer’s disease patients. The study, published in Nanoscale, has shed light on the way in which metallic species contribute to the pathogenesis of Alzheimer’s disease and could help direct future therapies.

Alzheimer’s disease is a neurodegenerative disease that is associated with dementia and shortened life expectancy. The disease is characterised by the formation of protein plaques and tangles in the brain that impair function. As well as protein plaques, perturbed metal ion homeostasis is also linked with pathogenesis, and iron levels in particular are elevated in certain regions of the brain.

A team of scientists with a long history in exploring biomineralisation in Alzheimer’s brains set out to characterise the iron species that are associated with the amyloid protein plaques. They extracted samples from the brains of two deceased patients who had Alzheimer’s and applied synchrotron X-ray spectromicroscopy to differentiate the iron oxide phases in the samples.

They noted evidence that the chemical reduction of iron, and indeed the formation of a magnetic iron oxide called magnetite, which is not commonly found in the human brain, had occurred during amyloid plaque formation, a finding that could help inform the outcomes of future Alzheimer’s therapies.

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Image: Synchrotron soft X-ray nano-imaging and spectromicroscopy reveals iron and calcium biomineralisation in Alzheimer’s disease amyloid plaques.