Experimental approaches for the pathogenic understanding of Alzheimer's disease. Effect of b-amyloid-metal ions complexes in in vitro and in vivo models

Alzheimer's disease (AD) is classified as a conformational disease and is characterized by tissue insoluble deposits as a consequence of proteins aggregation. In AD brain, two different features of protein deposition are identified: intracellular neurofibrillary tangles and extracellular senile plaques. Several studies in literature paid attention to the main component of senile plaques: beta-amyloid peptide, which aggregates in various structures with the final formation of insoluble fibrils, typical of senile plaques. A huge number of reports indicate that, among putative aggravating factors, metal ions (Al, Zn, Cu, Fe) could specifically impair protein aggregation of Abeta and their oligomeric toxicity.The aim of this thesis is to investigate the effect of various Abeta-metal complexes, in comparison with Abeta alone, in various experimental models both in vitro and in vivo. The experimental approach is completely new with respect to other studies in literature where the Abeta and metal ions toxicity have been separately evaluated and not as a complex as Abeta-metals. This complex could better reproduce the same neuronal environmental condition as observed in the pathological events.