Figure 9.

Possible Aβ-dependent and Aβ-independent mechanisms of neurotoxicity. In this model, 1 route toward neurotoxicity begins with either APP mutations or PS1 mutations (top center of figure). The pathway toward toxicity flows downward via elevated Aβ42 levels and elevated oligomer levels. An alternative pathway is shown on the right side of the figure, whereby superoxide (O₂^•–) or hydrogen peroxide (H₂O₂) oxidize lipids such as prostaglandins, forming F_2α-isoprostanes. Both H₂O₂ and F_2α-isoprostanes are known to accelerate Aβ aggregation and presumably its oligomerization. This author proposes that toxicity in this pathway occurs both directly from reactive oxygen species (H₂O₂ and O₂^•–) and via acceleration of Aβ oligomerization by these reactive oxygen species.