MAPT and Alzheimer disease: However, based on studies on AD or other pathologies, two hypotheses have been proposed: (i) Modified forms of tau could induce increased ROS production and higher calcium concentrations (Panel et al., 2018; Perez et al., 2018a), which could result in mitochondrial dysfunction and ultimately in mPTP opening; (ii) Tau may interact with mitochondrial proteins (Liu et al., 2016), such as CypD (Amadoro et al., 2010) promoting mitochondrial failure and a more active mPTP.