Barthet and Mulle highlight three main presynaptic mechanisms possibly affected in the AD synaptopathy: (i) APP fragments binding to presynaptic receptors (e.g., nAChRs and GABABRs), (ii) presenilins controlling Ca2+ homeostasis and Ca2+-sensors and (iii) tau regulating the localization of synaptic vesicles and presynaptic molecules (Barthet and Mulle, 2020). This evidence concerns the gene APP and Alzheimer disease.