MAPT and Alzheimer disease: However, transport defects can occur independent of tau and before overt morphologic decline and cell death, suggesting that early transport defects might play a causal role in AD pathogenesis (Pigino et al., 2003; Lazarov et al., 2007; Stokin et al., 2008; Goldstein, 2012; Rodrigues et al., 2012; Ramser et al., 2013).