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With rapidly ageing populations, dementia caused by neurodegenerative diseases has become a global socioeconomic issue. Globally, more than 24 million people were suffering from dementia in 2005 (C. Ferri et al.,2005). Alzheimer’s disease (AD) is the most common cause of dementia. While characterized by the presence of Amyloid-beta () peptide plaques in the brain (Masters and Beyreuther, 2006), a major source of the neurotoxicity in AD is now believed to be due to the action of soluble  oligomers (Crouch et al., 2008).  is generated from the amyloid precursor protein (APP) by the action of and secretases, and yields peptides 39-43 amino acid residues long, with (1-40) and (1-42) the most common. (1-42) has the primary sequence D1AEFRH6DSGY10E11VH13H14QK16LVFFAEDVGSNK28GAIIGLM35VGGVVIA42). Structural characterization of the formation of the  oligomers is currently the subject of intensive research. Among the possible mechanisms are those mediated by the interaction of  with metal ions. This includes both redox-active metals such as Copper, and Iron, as well as redox-inactive metals such as Zinc. For example, interaction of Cu(II) (i.e. Cu2+) with  in the presence of reducing agents leads to the production of reactive oxygen species (ROS). This in turn can generate toxic soluble  oligomers via the formation of di-tyrosine crosslinked  dimers (Barnham et al., 2004). The Copper-chelating compound PBT2 has shown efficacy and safety in Phase IIa clinical trials (Adlard et al., 2008). More recently, Platinum and Ruthenium compounds have been synthesized and shown to ablate -mediated neurotoxicity. Clearly, interaction of metals with  plays an important role in the aetiology of AD and is very relevant to the design of effective therapeutics. Knowledge of the atomic structure of metals bound to the  peptide would greatly facilitate the design of such chemical entities and assist in the elucidation of the mechanisms of neurotoxicity.

Structural and Computational Studies of Interactions of Metals with Amyloid Beta