Primary cultures of neurons from AD transgenic mice have replicated in vivo phenotypes seen in AD, including increased endosome size (Willén et al., 2017) and loss of spines (Kashyap et al., 2019), and have shown Aβ-dependent reductions in important synaptic proteins, such as glutamate receptors, PSD-95 and synaptophysin (Almeida et al., 2005). Here, DLG4 is linked to Alzheimer disease.