Our data suggested that abnormally upregulated PI3K signaling can forcefully increase tau phosphorylation at the two Akt sites that may play a key role in the pathogenesis of tauopathies, a notion that is supported by the observation that a higher Akt activity and loss of PTEN are indeed found in postmortem AD brains [25,43]. This evidence concerns the gene MAPT and tauopathy.