Intracellular Trafficking Mechanisms of Synaptic Dysfunction in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive memory loss. Although AD neuropathological hallmarks of extracellular amyloid plaques and intracellular tau tangles, which best correlates of disease progression is the loss of synapses. What causes the loss of synapses have been the focus of some researchers in the field of AD. Synapses become dysfunctional before the plaques and tangles form. 

The study is based on the model of early-onset familial AD (eFAD) has supported that synaptic transmission depressed by β-amyloid (Aβ) triggered mechanism. Since eFAD rare, affecting only 1% of patients, research has shifted to the study of the most PBS  common late-onset AD (LOAD). intracellular trafficking has emerged as one of the pathways of gene LOAD. 

Several studies have assessed the impact of gene LOAD trading on synapse dysfunction. Because the endocytic traffic is very important for synaptic function, we review the mechanism of Aβ-dependent and independent of the earliest synaptic dysfunction in AD. 

We have focused on the role and secreted intraneuronal Aβ oligomers, highlighting dysfunction endocytic trafficking as Aβ dependent mechanism of synaptic dysfunction in AD. Here, we review LOAD trafficking APOE4 gene, ABCA7, BIN1, CD2AP, PICALM, EPH1A, and SORL1, which is no synaptic link. We conclude that in eFAD and LOAD, early synaptic dysfunction characterized by disruption of presynaptic vesicle exo- and reverse endocytosis and postsynaptic glutamate receptor endocytosis. 

While in eFAD synapse dysfunction seems to be triggered by Aβ, in LOAD, there may be a direct synaptic gene disruption LOAD trading. To identify promising therapeutic target and biomarker earliest synaptic dysfunction in AD, it will be necessary to join efforts to further dissect the mechanisms used by Aβ and the LOAD genes disrupt synapses.