APP and Alzheimer disease: Synaptic disruption in AD can be induced by both extracellular Aβ1-42 oligomers and intracellular hyperphosphorylated Tau, and as such, may be connected to other aspects of AD neuropathology, such as altered APP processing, abnormal phosphorylation, and calcium imbalance (Yao, 2004; Pei et al., 2020; Hori et al., 2022; Ratan et al., 2023).