MECHANISMS ON INTRACELLULAR ACCUMULATION OF AMYLOID BETA PEPTIDE LEADING TO CELL DEATH

Alzheimer’s disease has been thought to be caused by cellular accumulation of amyloid beta peptide (Aβ) that was produced in extracellular space. The mechanisms by which extracellular accumulation of Aβ42, which is a toxic form of Aβ peptide, leads to cell death have been well-examined. Recently, intracellular accumulation of Aβ42 has also been observed, however, the mechanism by which intracellular Aβ42 accumulation causes cell death is still unknown. In this study, we investigated the mechanism of cellular toxicity caused by Aβ42 accumulated in cells. After chemically synthesized Aβ42 was incubated with cells, intracellular localization of Aβ42 incorporated into cells was examined by co-localization with several organelle marker proteins. It was reported that oligomeric Aβ generated reactive oxygen species (ROS) in vitro. And effect of overexpression of an anti-oxidative enzyme on cell viability under the Aβ42 treatment was also examined to reveal relationship between ROS production caused by intracellular Aβ42 accumulation and cell death.