Role of metal ions in amyloid-beta oligomer formation in AD

Australia's Prana Biotechnology, a specialist in the field age-related neurodegenerative disorders, says data indicates that biological metals such as copper and zinc can bring about conformational changes in the beta-amyloid protein (ABeta) associated with Alzheimer's disease, causing it to adopt a range of toxic forms.

The work was presented in an article entitled "Engineering metal ion coordination to regulate amyloid fibril assembly and toxicity" in a recent edition of the journal, Proceedings of the National Academy of Sciences. The authors, led by David Lynn, reported that subtle variations in the chemical environment of the brain can influence the binding of copper ions to certain domains of ABeta, altering its ability to form both fibrillar and oligomeric structures. Since oligomeric forms of ABeta represent one of the best validated targets for AD treatment, the team believes that its work is of considerable value.

Prof Lynn's group also reported that, because metal ion binding is thought to be an important factor in other neurodegenerative conditions, including Parkinson's disease, the findings may prove beneficial in the development of new therapies. PBT2, Prana's lead drug candidate which is currently in Phase IIa AD trials, was designed to inhibit the formation of toxic ABeta oligomers by limiting the protein's interactions with copper and zinc.