GAB2 and Neurofibrillary tangles: Based on this finding and along with the fact that Gab2 is the principal activator of the phosphatidylinositol 3-kinase signaling pathway [30], activation of which suppresses glycogen synthase kinase 3-mediated phosphorylation of tau and prevents apoptosis of confluent cells [31], Reiman et al hypothesized that Gab2 might function to protect neurons from neurofibrillary tangle formation and that a loss-of-function GAB2 haplotype would increase tau phosphorylation at sites abnormally phosphorylated in AD brains.