Fig. 5: Model for enhanced synaptotoxicity caused by the combination of Aβ oligomers and slowed synaptic vesicle endocytosis.
From: A delay in vesicle endocytosis by a C-terminal fragment of N-cadherin enhances Aβ synaptotoxicity
Left: Transsynaptic N-cadherin interactions have a crucial role in enabling fast synaptic vesicle endocytosis. Upper right: Fast synaptic vesicle endocytosis does not allow for efficient uptake of toxic Aβ oligomers during a 2 days incubation, because Aβ oligomer binding to its intraluminal membrane receptors might be a very slow process. Lower right: Disturbing transsynaptic N-cadherin interactions by increased presence of N-cadherin-CTF1 leads to a slow down of synaptic vesicle endocytosis. Slow down of endocytosis in turn increases Aβ oligomer uptake, because slow Aβ binding can now take place before vesicle endocytosis is completed. Intracellular Aβ might then induce synaptotoxic effects.
