While it is known that Tau binds to presynaptic proteins and contributes to synapse dysfunction in AD (McInnes et al. 2018; Tracy et al. 2022; Zhou et al. 2017), we provide the first evidence that presynaptic interactions are isoform‐specific and that 0N4R‐Tau specifically binds signaling proteins modulating the exocyst‐dependent exocytosis and RAB11 protein function. Here, MAPT is linked to Alzheimer disease.