Figure 4.

Effect of Aβ in MERCS under normal and AD conditions. Schematic representation of what happens in the cell upon an increase in Aβ levels in normal and AD conditions. Under normal conditions, an increase in Aβ leads to an increase in the connectivity between the ER and mitochondria, affecting MERCS ultrastructure and function. Together, the increased connectivity and altered function of MERCS prevent further Aβ formation. However, when the levels of Aβ are too high, this negative feedback loop is not enough to decrease the levels of this peptide. Aβ continues to induce an increase in the connectivity between the ER and mitochondria, which culminates in Ca²⁺ overflow into mitochondria, activating cell death. Arrows point up correspond to up-regulated and arrows point down down-regulation. Two arrows side-by-side correspond to a further increase or decrease biological process as compare to normal conditions.