In situ characterization and mapping of iron compounds in Alzheimer's disease tissue

Abstract

There is a well-established link between iron overload in the brain and pathology associated with neurodegeneration in a variety of disorders such as Alzheimer's (AD), Parkinson's (PD) and Huntington's (HD) diseases [1]. This association was first discovered in AD by Goodman in 1953 [2], where, in addition to abnormally high concentrations of iron in autopsy brain tissue, iron has also been shown to accumulate at sites of brain pathology such as senile plaques [3]. However, since this discovery, progress in understanding the origin, role and nature of iron compounds associated with neurodegeneration has been slow. Here we report, for the first time, the location and characterisation of iron compounds in human AD brain tissue sections. Iron fluorescence was mapped over a frontal-lobe tissue section from an Alzheimer's patient, and anomalous iron concentrations were identified using synchrotron X-ray absorption techniques at 5 µm spatial resolution. Concentrations of ferritin and magnetite, a magnetic iron oxide potentially indicating disrupted brain-iron metabolism, were evident. These results demonstrate a practical means of correlating iron compounds and disease pathology in-situ and have clear implications for disease pathogenesis and potential therapies.

Biometals and Their Therapeutic Implications in Alzheimer's Disease

“…Iron elevation in AD brains, first demonstrated in 1953 [99], is a consistently reported finding [99][100][101][102][103][104][105][106][107][108]. Neuronal iron deposition causes oxidative stress via the Fenton reaction, which might contribute to elevated oxidative stress observed in the AD brain [109].…”

Mineralization of the Deep Gray Matter with Age: A Retrospective Review with Susceptibility-Weighted MR Imaging

“…34 Because SWI lacks chemical sensitivity, the interpretation of SWI image intensity may be improved through comparison with the XAS maps of metals. In addition, the high resolution achievable with XAS imaging may uncover new information about the co-localization and deposition of different metals, and about pathways of metal storage in the brain.…”

Iron: The Redox-active Center of Oxidative Stress in Alzheimer Disease

“…Later that same year, Collingwood et al [62,63] demonstrated the application of this technique to AD tissue sections. This work provided the first map of iron distribution in AD tissue in which specific iron anomalies (areas of high iron concentration) were not only located but characterized with 5 lm spatial resolution.…”