Looking for biogenic magnetite in brain ferritin using NMR relaxometry

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Abstract

Mammalian cellular iron is stored inside the multisubunit protein ferritin, normally taking the structure of a ferrihydrite-like mineral core. It has been suggested that biogenic magnetite, which has been detected in the brain and may be related to neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, could initially form in ferritin. Indeed, as ferritin is present in the brain, the ferrihydrite core could be a precursor for biogenic magnetite formation--particularly in cases where the normal functioning of the ferritin protein is disrupted. In this work, NMR relaxometry was used to detect magnetite inside samples of ferritin extracted from normal and Alzheimer-diseased brains. The method was first calibrated with different fractions of horse spleen ferritin and synthetic magnetite particles. The relaxometry results suggest that the proportion of iron contained in brain ferritin in the form of well-crystallized magnetite instead of ferrihydrite must be <1%, which is much less than that reported for 'magnetite-like' phase in recent transmission electron microscopy studies of similar samples. Consequently, the magnetization of this 'magnetite-like' phase must be very low compared with that of magnetite.

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