Tau can associate cell plasma membrane by its N-terminal region [82] without altering its microtubules binding. Tau can be phosphorylated by Fyn, a tyrosine kinase from the nonreceptor Src family kinases [83]. Fyn participates in the signal transduction system related to integrins having responses such as the Ras and Rho activations and the consequent actin reordering [84]. Bhaskar et al [85] have shown that Src also phosphorylate tau in Tyr 18 in vitro. In addition, Derkinderen et al [86] demonstrated that Abl phosphorylates tau in Tyr 394; both phosphorylations are present in PHFs. Tyr 18 is conserved in all tau isoforms and the sequence around this residue (GTYG) is close to the binding sequence of Fyn to its target (ETYG). Among the 7 PXXP motifs of tau, one has the major affinity to Fyn SH3 domain [84]. Moreover, Fyn has more affinity for 3R tau than for 4R tau, however, the low affinity for 4R tau is considerably increased by phosphorylations present in AD-like Ser 199/Ser202 and Ser 396/Ser 404, epitopes recognized by AT8 and PHF1 antibodies [85]. Since tau 3R plays an important role in neuronal development, its affinity with Fyn has a major function in this process. Meanwhile, tau 4R is mainly present in adult brain, and the increase in its affinity for Fyn may have an important effect in AD etiopthogenesis (Figure 1).