OO004 - ELEMENTAL METALLIC NANOPARTICLES IN ALZHEIMER’S BRAINS (ID 1687)

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Abstract

Aims

Altered metal homeostasis has been linked to the development of multiple neurodegenerative disorders including Alzheimer’s disease. However, our knowledge of metal (bio)chemistry in Alzheimer’s lacks the chemical and spatial detail required to understand how metals contribute to disease pathogenesis, preventing the development of effective metal-targeting technologies for disease diagnosis/treatment. Here, synchrotron x-ray microscopy and spectroscopy were used to characterize the nanoscale chemistry of metal inclusions within amyloid plaques from Alzheimer’s brains.

Methods

Amyloid plaques from two Alzheimer’s brains were examined using scanning x-ray fluorescence (XRF) at Diamond Light Source beamline I14, and scanning transmission x-ray microscopy (STXM) at Diamond beamline I08 and Advanced Light Source beamline 11.0.2. XRF maps were collected at 80 nm resolution showing the elemental composition of the plaques. STXM was performed over the copper and iron L­-edges at ~50 nm spatial resolution to determine the chemical state of these metals.

Results

Amyloid plaques were found to harbour iron, copper, zinc, nickel, mercury, calcium and potassium at levels detectable by nanofocus XRF. STXM examination of the plaques revealed nanodeposits of elemental metallic Cu0 accompanying ferromagnetic elemental Fe0, previously undocumented in human biology.

Conclusions

Metallic Cu(0) and Fe(0) have distinctly different chemical and magnetic properties from their Cu(I/II) and Fe(II/III) forms in which they are predominately utilized in tissues, and their highly reactive surfaces may generate free radicals and other active species. The discovery of elemental metals in the brain raises new questions regarding their generation and their role in neurochemistry, neurobiology, and the etiology of neurodegenerative disease.

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