The stabilization of ferrous iron by a toxic beta-amyloid fragment and by an aluminum salt

Aluminum is a recognized neurotoxin in dialysis encephalopathy and may also be implicated in the etiology of neurodegenerative disease, particularly A lzheimer's disease. Alzheimer's disease is suspected to be associated with oxidative stress, possibly due to the pro-oxidant properties of beta-amyloi d present in the senile plaques. The underlying mechanism by which this occ urs is not well understood although interactions between amyloid and iron h ave been proposed. The presence of low molecular weight iron compounds can stimulate free radical production in the brain. This study provides a possi ble explanation whereby both aluminum and beta-amyloid can potentiate free radical formation by stabilizing iron in its more damaging ferrous (Fe2+) f orm which can promote the Fenton reaction. The velocity, at which Fe2+ is s pontaneously oxidized to Fe3+ at 37 degrees C in 20 mM Bis-Tris buffer at p H 5.8, was significantly slowed in the presence of aluminum salts. A parall el effect of prolongation of stability of soluble ferrous ion, was found in the presence of beta-amyloid fragment (25-35). Ascorbic acid, known to pot entiate the pro-oxidant properties of iron, was also capable of markedly st abilizing ferrous ions. (C) 1999 Published by Elsevier Science B.V. All rig hts reserved.