About the presence of hemosiderin in the hippocampus of Alzheimer patients.

Ferritin and Hemosiderin (Hm) are the iron-storing “elements” in cells. Whereas Ferritin is a wellcharacterized soluble protein that has been extensively studied [1–5], the term Hemosiderin does not have the same clarity of meaning for the pathologist, biochemist or electron microscopist. For the pathologist [6], Hm represents iron-containing conglomerates, stainable with Perl’s stain. For the biochemist, Hm is a heterogeneous insoluble compound, containing iron, proteins, carbohydrates and lipids. For the electron microscopist, Ferritin and Hm are nanoparticles (5– 7 nm in diameter), recognizable because of the electrondensity of the iron concentrated in their “cores”. Hm has been observed in various tissues and organs, including the liver, spleen, heart, intestines, pancreas and tumors (neuroblastomes), associated with ironoverload pathologies such as primary (PH) and secondary (SH) hemochromatosis and transfusional or local bleeding siderosis [6–8]. Hm is considered a product of degradation of Ferritin localized within siderosomes [4,7]. In Ferritin, iron is mainly stored as ferrihydrite, hydrated Fe iron oxide nanocrystals [1– 3]. In Hm, several different iron oxyhydroxide mineral structures have been identified depending on the disease [9–11]. By employing electron microscopy, Hm can be distinguished from Ferritin when individual particles cannot be resolved or when they come closer than 13 nm (the mean external diameter of one Ferritin protein shell [2]). We have observed, using electron microscopy, Hm in the hippocampus of AD patients [12,13]. Figures 1 and 2 show two examples of Hm rich-regions: (1) the cytoplasm of oligodentrocytes near the nuclei; in these cells Ferritin is often observed in the nucleoplasm [12, 13] and (2) the oligodendrocyte processes associated with myelinated axons devoid of abnormal accumulations of filaments [13]. These oligodendrocyte processes also contain numerous Ferritin molecules and the myelin sheaths of these axons are frayed. What could be the role of Hm in oligodendrocytes ? Let us remind ourselves of some of the known roles of iron in the brain.