beta-Amyloid deposits, hallmarks of Alzheimer's disease, contain both sugar
-derived 'advanced glycation end products' (AGEs) and copper and iron ions.
Our in vitro experiments using synthetic beta-amyloid peptide and glucose
or fructose show that formation of covalently cross-linked high-molecular-m
ass beta-amyloid peptide oligomers is accelerated by micromolar amounts of
copper (Cu+, Cu2+) and iron (Fe2+, Fe3+) ions. Formation of these covalent
AGE cross-links can be inhibited by capping agents of amino groups, redox-i
nactive metal chelators and antioxidants, suggesting that these drugs may b
e able to slow down the formation of insoluble beta-amyloid deposits in viv
o and possibly the progression of Alzheimer's disease.