Figure 1. Potential mechanisms leading to synaptic phosphatidylserine externalisation in Alzheimer’s disease.

Schematic representation of potential pathways by which oligomeric amyloid-beta and hyperphosphorylated tau may increase the vulnerability of synapses to loss in Alzheimer’s disease. Synaptic mitochondrial dysfunction may lead to a build-up of cleaved caspase-3, reactive oxygen species (ROS) and Ca²⁺, accompanied by a decrease in ATP. These events can modulate the activity of flippases and scramblases, enzymes which regulate the localisation of phosphatidylserine (PtdSer), such that PtdSer is locally externalised to the outer leaflet of synaptic membranes. ePtdSer, externalised phosphatidylserine.