Figure 4

Synaptic element interdependence model of synaptic maintenance, reorganization, and Alzheimer's disease. The pre-synaptic and post-synaptic elements are interdependent, and provide both trophic influences (e.g., neurotrophins, netrin-1, laminin, collagen, and synaptic activity itself) and anti-trophic influences (e.g., amyloid-β peptide). Trophic support leads to the processing of APP into three peptides that support synaptic maintenance, whereas the withdrawal of trophic support leads to alternative processing, to four peptides that mediate synaptic inhibition, synaptic loss, neurite retraction, and ultimately, programmed cell death. In this model, the Aβ peptide functions as an anti-trophin, and, since it leads to APP processing that produces additional Aβ peptide, it is "prionic", i.e., Aβ begets additional Aβ.