The etiopathogenesis of
Alzheimer's disease is far from being clearly understood. However, the involvement of
metal ions as a potential key factor towards conformational modifications and aggregation of
amyloid is widely recognized. The aim of the present study is to shed some light on the relationship between
metal ions,
amyloid conformation/aggregation, and their potential relationship with the conformational aspects of AD. We compare the effects of beta-amyloid(1-42) and its various
metal complexes (
beta-amyloid-Al,
beta-amyloid-Zn,
beta-amyloid-Cu,
beta-amyloid-Fe) in human
neuroblastoma cells in terms of cell viability, membrane structure properties, and cell morphology. No significant toxic effects were observed in
neuroblastoma cells after 24h treatment both with
beta-amyloid and
beta-amyloid-metals (
beta-amyloid-Zn,
beta-amyloid-Cu,
beta-amyloid-Fe); on the other hand, there was a marked reduction of cellular viability
after treatment with
beta-amyloid-Al complex. In addition, treatment with
beta-amyloid-Al increased membrane fluidity much more than other
beta-amyloid-
metal complexes, whose contribution was negligible. Furthermore, the cellular morphology, as observed by electron microscopy, was deeply altered by
beta-amyloid-Al. Importantly,
beta-amyloid-Al toxicity is closely and significantly associated with a great difference in the structure/aggregation of this complex with respect to that of
beta-amyloid alone and other
beta-amyloid-
metal complexes. In addition,
beta-amyloid, as a consequence of Al binding, becomes strongly hydrophobic in character. These findings show a significant involvement of Al, compared to the other
metal ions used in our experiments, in promoting a specific amyloid(1-42) aggregation, which is able to produce marked toxic effects on
neuroblastoma cells, as clearly demonstrated for the first time in this study.