FIG. 2.

Akt1 phosphorylation and its kinase activity are decreased in synapses of APP/PS1 mice early in the disease pathogenesis. Levels of both the phosphorylated forms of Akt1 [Thr308; (A) and Ser473; (B)], which are critical for its kinase activity, are reduced in synaptosomes isolated from ADL and YA APP/PS1 mice compared with those from age-matched WT controls. Akt1 kinase activity was measured by immunoblot-based assay of phosphorylation of the Akt1 substrate, recombinant-truncated GSK [rec GSK; (C)]. Cortical synaptosomes from APP/PS1 mice have reduced Akt1 activity when compared with those from WT controls at all ages examined. Values are mean ± SEM (n = 6 mice) and * denotes values significantly different from corresponding controls (p < 0.05). See also Supplementary Fig. S1.