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Mutant PS1I213T knock-in mice used for these studies.

The following antibodies were used: mouse monoclonal anti-tubulin (DM1A, Sigma); anti-ubiquitin (Santa Cruz Biotechnology); anti-GSK3b (Transduction Lab); anti-MAP2 (HM2, Sigma); anti-tau Alz50, which recognizes the conformational epitope of paired helical filaments (PHFs), component of NFT (gift from Dr. P. Davies, Albert Einstein College of Medicine, Bronz, NY); anti-phosphorylated tau AT8 (Innogenetics); anti-dephosphorylated tau-1 (Chemicon); rabbit polyclonal anti-tau JM; anti-phosphorylated tau PS199, PS262, PS396, PS404, and PS422 (Biosource), which recognized tau phosphorylated at the indicated sites; and anti-GSK3b Ser-9 (Cell Signaling).