The Opt allele attenuates hippocampal Aβ and P-tau accumulation in 3xTg mice. A, Western blot analyses of hippocampal lysates from 3- to 18-month-old mice using antibodies specific for InsP3R1 (normalized to WT), hAPP (6E10), htau (HT7), htau phosphorylated at Ser-202 (AT8), or Thr-231 (AT180) with tubulin as a loading control. Representative blots are from experiments conducted on 18-month-old mice. Unpaired two-tailed t tests, n ≥ 3 mice each per age, *p < 0.05, **p < 0.005. B, ELISA of hippocampal homogenates for Aβ40 and Aβ42 in mice ranging in age from 6 to 18 months. Aβ content in homogenates from WT and Opt animals were always below the detection limit of the ELISA. Unpaired 2-tailed t test, n ≥ 5 mice each per age, *p ≤ 0.05, **p ≤ 0.005. Error bars show mean and SEM. C, Immunohistochemistry on hippocampal slices from 18-month-old mice for Aβ and P-tau. 6E10 intracellular staining is most likely full-length APP (Winton et al., 2011).