Figure 1b. Synaptic Aβ hypothesis.

Increased accumulation of synaptic Aβ oligomers promotes endocytosis of NMDA and AMPA receptors, leading to a reduction in dendritic spines and reduced long-term potentiation (LTP). Acceleration of this process could lead to a toxic gain of function in the form of an imbalance in the LTP/long-term depression (LTD) ratio. This, in turn, causes synaptic dysfunction, spine loss, and (potentially) synaptic loss, leading to cognitive decline and AD. AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; NMDA, N-methyl-d-aspartic acid.