Synaptic frailty and clathrin-mediated synaptic vesicle trafficking in Alzheimer's disease

Loss of synapses contributes to the progressive cognitive impairment in Alzheimer's disease. Emerging evidence suggests that synapses are not functioning optimally even before structural deterioration. Expression of synapse-specific proteins, including that of some involved in synaptic vesicle trafficking, is affected in the disease. This article reviews current understanding of these components in presynaptic functions and explores possible roles for aberrant synaptic vesicle trafficking in the dysregulation of synaptic function, an important aspect in the neuropathology of Alzheimer's disease. The inability of neurons to form synaptic vesicles properly could have direct consequences on the functionality of neuronal circuits. Further studies focusing on this possibility would be useful for understanding the disease process and could lead to therapeutic strategies that can modify the function of persistent synapses.