Abstract

We present a quantitative study of different molecular iron forms found in the temporal cortex of Alzheimer (AD) patients. Applying the methodology we developed in our previous work, we quantify the concentrations of non-heme Fe(III) by Electron Paramagnetic Resonance (EPR), magnetite/maghemite and ferrihydrite by SQUID magnetometry, together with the MRI transverse relaxation rate ({{rm{R}}}_{2}^{ast }), to obtain a systematic view of molecular iron in the temporal cortex. Significantly higher values of {{rm{R}}}_{2}^{ast }, a larger concentration of ferrihydrite, and a larger magnetic moment of magnetite/maghemite particles are found in the brain of AD patients. Moreover, we found correlations between the concentration of the iron detected by EPR, the concentration of the ferrihydrite mineral and the average iron loading of ferritin. We discuss these findings in the framework of iron dis-homeostasis, which has been proposed to occur in the brain of AD patients.

Highlights

  • Iron is an essential component of many enzymes and proteins that participate in a variety of biological functions in the brain, such as neurotransmitter synthesis and myelination of neurons[1]

  • In contrast to previous studies, in which only one iron-oxide species was quantified, here we present a broad overview of iron forms obtained from a brain region where elevated iron concentration is found in Alzheimer’s Disease (AD)

  • Ferrihydrite concentration was significantly higher in the AD group (p = 0.007), while the ferritin loading ratio (FLR) was not significantly different between groups (p = 0.362)

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Summary

Introduction

Iron is an essential component of many enzymes and proteins that participate in a variety of biological functions in the brain, such as neurotransmitter synthesis and myelination of neurons[1]. It has been shown that magnetite and wüstite are both present in the AD brain[15]. This is of importance as such species possess Fe(II), which is associated with toxicity. These nanoparticles may be present in low concentrations[16], if they are larger than 40–50 nm in diameter, they carry a permanent magnetic moment at room temperature[14,15,17], which can significantly affect the proton Nuclear Magnetic Resonance Imaging (MRI) signal, allowing indirect imaging of iron[18,19,20]. Correspondence and requests for materials should be addressed to L.B

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