Aβ induces oxidative stress in senescence-accelerated (SAMP8) mice

According to the amyloid hypothesis, amyloid beta accumulates in brains with Alzheimer's disease (AD) and triggers cell death and memory deficit. Previously, we developed a rice A beta vaccine expressing A beta, which reduced brain A beta levels in the Tg2576 mouse model of familial AD. We used senescence-accelerated SAMP8 mice as a model of sporadic AD and investigated the relationship between A beta and oxidative stress. Insoluble A beta and 4-hydroxynonenal (4-HNE) levels tended to be reduced in SAMP8 mice-fed the rice A beta vaccine. We attempted to clarify the relationship between oxidative stress and A beta in vitro. Addition of A beta peptide to the culture medium resulted in an increase in 4-HNE levels in SH-SY5Y cells. Tg2576 mice, which express large amounts of A beta in their brain, also exhibited increased 4-HNE levels; this increase was inhibited by the A beta vaccine. These results indicate that A beta induces oxidative stress in cultured cells and in the mouse brain.