Beta-amyloid and oxidative stress jointly induce neuronal death, amyloid deposits, gliosis, and memory impairment in the rat brain

Infusion of Fe2+, A beta(42), and buthionine-sulfoximine (FAB), but not A beta(42) alone or in combination with Fe2+, into the left cerebral ventricle of Long-Evans rats for 4 weeks induced memory impairment that was accompanied by increased hyperphosphorylated Tau protein levels in the CSF. FAB-infused animals displayed thioflavin-S-positive amyloid deposits, hyperphosphorylated Tau protein, neuronal loss, and gliosis. Animals treated with A beta(42), Fe2+, or buthionine- sulfoximine alone or in combination failed to show the histological modifications seen with FAB. This data suggests that A beta(42) is not sufficient to induce an Alzheimer's disease-like symptomatology, and it supports a model whereby a decrease in the brain's antioxidant defense system leads to the A beta(42)-independent oxidative stress necessary for the peptide to induce histopathological changes and memory loss. Copyright (C) 2006 S. Karger AG, Basel.