Pathologic modifications of the presynaptic neurotransmitter-releasing machinery and/or altered expression of specific postsynaptic proteins, such as the postsynaptic density protein-95 (PSD-95), are at the basis of the synaptic impairment observed in AD (Sheng et al., 2012; Südhof, 2012, 2013). Here, DLG4 is linked to Alzheimer disease.