Antibodies used for Western blot or immunoprecipitation were: anti-Flag M2 (Sigma), anti-Ab 6E10 (Signet Labs), Ab14 (for PS1 NTF, 1:2000), Ab13A11 (for PS1 CTF, 5 µg/ml), and nicastrin antibodies (gift of St. George-Hyslop and D. Miller, 1:2500). In addition, polyclonal antisera directed against PS2 NTF (2972) (gift of C. Haass), PS-associated protein (PSAP) (gift of X, Xu), calsenilin (gift of W. Wasco), monoclonal antibodies to b-catenin (BD Transduction Laboratories) and APP 8E5 and APP 13G8 were used. PS1 or nicastrin coimmunoprecipitations were performed by using anti-sera X81 (raised to the first 81 residues of the PS1 NTF) or R302 (raised to the last 12 residues of nicastrin).