Working hypothesis.

Aβ-Cyclphilin D mediates impairments in axonal mitochondrial transport. In the present of Aβ, there is an increase in the opening of CypD-mediated mitochondrial permeability transition pore (mPTP), leading to disruption of Ca²⁺ balance and increase in reactive oxygen species (ROS) production/accumulation. Consequently, elevation of Ca2+ and oxidative activates downstream signal pathway p38 MAP Kinase contributing to mitochondrial dysfunction, deficits in axonal mitochondrial trafficking, eventually, synaptic damage.