SHANK3 and Alzheimer disease: Research evidence indicates that the massive SHANK3 protein (at ~185 kDa) forms an extensive post-synaptic cytoskeletal scaffolding network (involving the linkage of multiple SHANK3 proteins at the PSD) to which the smaller PSD-95 (at ~95kDa) protein is tethered usually via the SAPAP protein (~100 kDa); interestingly both SHANK3 and PSD-95 proteins, highly interactive components of the PSD complex, are reduced in abundance in the temporal lobe of AD-affected brain (13, 19, 20).