C. Rossi

Possible relationship between Al/ferritin complex and Alzheimer's disease

OBJECTIVES Ferritin is the main iron-storage protein capable of containing thousands of iron atoms. However, ferritin can bind in vitro other atoms such as aluminum and it has been shown that also in vivo atoms other than iron, as aluminum and zinc, are present in large amounts in ferritin. Since aluminum appears to be involved in the development of Alzheimers disease, in the present study the specific content of aluminum in ferritin of Alzheimers patients was analyzed and compared with other control groups. DESIGN AND METHODS The content of Fe, Al and Zn of blood ferritin was measured by mass spectrometry in patients with Alzheimers disease and compared with other clinical and control groups. RESULTS The results obtained confirm the hypothesis of a functional role of ferritin as a regulatory protein of toxic metals and clearly indicate that ferritin from Alzheimers patients has a content of aluminum higher than that of controls. CONCLUSIONS The specific aluminum content of ferritin seems to be related to different disease stages of Alzheimers disease. This result confirms the hypothesis of aluminum as a possible factor inducing the Alzheimers disease and opens the ways to possible new diagnostic tests.

Transient state kinetic investigation of ferritin iron release

Increased iron concentration in tissues appears to be a factor in the genesis and development of inflammatory and degenerative diseases. By means of real-time small angle x-ray scattering measurements, we studied the kinetics of iron release from the ferritin inorganic core as a function of time and distance from the iron core centre. Accordingly, the iron release process follows a three step model: (i) a defect nucleation in the outer part of the mineral core, (ii) the diffusion of the reducing agent towards the inner part of the core, and (iii) the erosion of the core from the inner to the outer part.

Ferritin iron content in haemodialysis patients : Comparison with septic and hemochromatosis patients

OBJECTIVES Hemodialysis (HD) population commonly show high plasma ferritin levels with a poor diagnostic value. The objective of this study is to elucidate the meaning of HD hyperferritinemia through the analysis of its ferritin iron content (FIC). DESIGN AND METHODS FIC (iron atoms/ferritin molecule) was measured by atomic emission spectrometry. Ferritin and FIC values were correlated with iron storage and inflammation markers and the results of HD patients compared to those of septic and hemochromatosis patients. RESULTS 1) In the whole HD population, high ferritin levels were associated to low FIC values; 2) the correlation of ferritin with iron indices and inflammation markers in HD patients was intermediate in between that of septic and hemochromatosis patients; 3) the FIC level of HD patients was lower than that of the other two groups. CONCLUSIONS The high ferritin levels of HD patients are not synonymous with either inflammation or of high levels of iron storage. Their high levels and the low FIC values might be due to the presence inside the ferritin core of oligoelements other than iron.

Mechanism of aluminium bio-mineralization in the apoferritin cavity

Many experimental evidences point out the correlation between the presence of aluminum-ferritin complex and neursopathological disorders. In these complexes, two different ranges of Aluminium (Al) atoms are usually found, i.e., just few atoms or several hundreds. Here, we investigated the in-vitro Al-apoferritin binding, with the aim to elucidate the mechanism behind the formation of Al-ferritin complexes in-vivo. To this purpose, we studied the mineralization of Al in its ionic and complexed form with citrate demonstrating that high Al levels found in clinical studies can be obtained only conveying Al by small physiological ligands.

Iron, zinc and aluminium ferritin content of hemodialysis hyperferritinemic patients: Comparison with other hyperferritinemic clinical conditions and normoferritinemic blood donors

The present study describes the specific content of ferritin iron, zinc and aluminium in four different groups: 1) hemodialysis hyperferritinemic patients; 2) septic patients; 3) iron overloaded patients with hematologic diseases; and 4) blood donors. In all four groups high levels of aluminium and zinc were found in addition to those of iron. However, the sum of the ferritin ions of the control group is significantly higher than that of the other three groups. Furthermore, while ferritin of hemodialysis patients has the same molecular ratio of metal ions as control group (high Al content vs. Fe and Zn), a lower Al/Fe ratio is found both in septic and hematological patients. The results of the present paper might help to explain the high percentage of hyperferritinemia found in hemodialysis patients also in presence of low transferrin saturation and in absence of inflammatory markers. Moreover, the high content of ions other than iron in the ferritin core leads us to believe that ferritin is not only an iron storage protein but rather a regulator of redox active ions.

The APOE-491 A/T promoter polymorphism effect on cognitive profile of Alzheimer's patients.

Alzheimers Disease (AD) is a neurodegenerative disorder with a complex aetiology displayed by multiple pathogenic factors. The APOE varepsilon4 allele represents the only established genetic risk factor for sporadic AD; in addition, previous findings on three single nucleotide polymorphisms (SNPs) located on the APOE promoter region, have led to a growing interest in their potential role in AD pathogenesis. The -491 A/T promoter polymorphism has been the one most frequently shown to be associated with AD, as it influences the APOE coding region transcription. The aim of this study was to evaluate the possible effect of the -491 A/T polymorphism on the cognitive profile of sporadic AD patients with a disease severity ranging from mild to moderate. Our results showed that patients carrying the -491 AA genotype had poorer cognitive performances than the -491 AT ones, statistically significant in demanding tests of visual attention, especially for the late-onset AD (LOAD). No further differences on cognitive profile were observed when stratifying AA and AT patients according to their APOE genotype. These results suggest a possible functional effect of the -491 A/T promoter on the neuropsychological performances of AD. This role seems to be independent of APOE genotype. In fact the effect of -491 A/T occurs predominantly on attention while the APOE varepsilon4 allele mainly affects memory performances. According to the biological effect exerted on APOE transcription, the -491 A/T polymorphism could be considered a disease modifier more than a risk factor for sporadic AD.