Iron and aluminium in relation to brain ferritin in normal individuals and Alzheimer's-disease and chronic renal-dialysis patients

Abstract

Ferritin has been isolated and its subunit composition, iron and aluminium content determined in the cerebral cortex and cerebellum of normal individuals and in the cerebral cortex of Alzheimer's-disease and renal-dialysis patients. An e.l.i.s.a. for ferritin has been developed and the ferritin, non-haem iron and aluminium content of the parietal cortex were determined in normal individuals and Alzheimer's-disease patients. It was found that ferritin from the cerebral cortex and cerebellum of normal individuals had a high H-subunit content, similar to that of heart ferritin. The subunit composition of ferritin isolated from the cerebral cortex was not significantly altered in Alzheimer's-disease or renal-dialysis patients. Ferritin from the cerebral cortex of normal individuals had only approx. 1500 atoms of iron per molecule and the iron content of ferritin was not significantly changed in Alzheimer's-disease or renal-dialysis patients. Ferritin isolated from the cerebral cortex of normal, Alzheimer's-disease and renal-dialysis patients had less than 9 atoms of aluminium per molecule. The failure to find increased concentrations of aluminium associated with ferritin in dialysis patients, who had markedly increased concentrations of aluminium in the cerebral cortex, shows that aluminium does not accumulate in ferritin in vivo. This has important implications for the toxicity of aluminium, since it implies that cells are unable to detoxify aluminium by the same mechanism as that available for iron. Comparison of the concentrations of ferritin, aluminium and iron in the parietal cortex from normal and Alzheimer's-disease patients showed that, whereas the concentration of aluminium was not increased, both ferritin and iron were significantly increased in Alzheimer's disease.

The promotion of iron-induced generation of reactive oxygen species in nerve tissue by aluminum

“…Both proteins were in the iron-loaded form. Ferritin normally contains some complexed aluminum (Dedman et al, 1992), which can modulate its properties (Fleming and Joshi, 1991). Transferrin has a high affinity for, and may transport aluminum into the central nervous system (CNS) (Roskams and Connor, 1990).…”

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

“…3 A growing body of data suggests that brain iron accumulation in vivo may contribute to tissue damage in a variety of chronic neurological disorders. Histological and magnetic resonance imaging (MRI) data have suggested increases in iron levels in the gray matter in Parkinson's disease (PD), 4 -10 Alzheimer's disease (AD), [11][12][13][14][15][16][17] multiple sclerosis (MS), 18 -21 and a host of other chronic neurological disorders. 22 Consequently, there is a growing interest in optimizing the ability of MRI to estimate iron deposition in vivo.…”

Mechanism of aluminium bio-mineralization in the apoferritin cavity

“…By the way, the mechanism behind the Al complex formation in vivo is still controversial also because two different ranges of Al bound to ferritin have been generally found: few atoms in some studies 5,6 and hundreds or even thousands in others. 3,4,9 Furthermore in this latter case also a very high Al/Fe molar ratio has been observed (in some specific case up to 6).…”

“…4 Subsequent studies carried on ferritin isolated from brain of renal dialysis patients showed an amount of 10 Al atoms per ferritin molecule. 5 Ward et al reported a small amount of the radioactive tracer 26 Al associated with liver ferritin of Al loaded rat. 7 The total Al amount per ferritin molecule found in the these studies is of the same order as the one shown in Fig.…”

“…1 Although ferritin has its main role in iron storage, several evidences suggest that it functions as a general metal detoxicant, binding in-vivo metals other than iron, such as aluminium (Al), 2-7 which has been recognized as a contributing factor in several neurological disorders. 8 The frequent isolation of Al-ferritin complexes, especially from Alzheimer Disease (AD) patients, 3,5,9,10 contributes to strengthen the suggested role for ferritin in metal toxicity. The observed increase of Al bound to brain ferritin has been indeed proposed as a detoxification mechanism which protects the brain metabolism from Al that cannot be cleared by other mechanisms.…”