Fig. 7.

AICD levels are increased in human AD brains. (A) Brain lysates from 13 AD patients (AD) and 12 non-dementia control subjects (Non-AD) were analyzed by SDS/PAGE and Western blotted with 0443 antibody (top rows) that recognizes APP-C terminus or AT-8 antibody (bottom rows). Blots were stripped and reprobed with GAPDH (middle rows). The upper rows show APP-CTF and AICD levels, which were quantified by NIH ImageJ software (B). Although there was a large variation in the AICD levels, they were significantly elevated in AD patients compared to non-demented controls (P = 0.0017). The lane marked with * in A (right panel) marks the non-AD sample with abnormally high AICD levels (an outlier). The wide variation in AD samples is also seen in phospho-tau levels. (C) Summary of pathological events observed in FeCγ25 mice. AICD expression is driven by a CaMKIIα promoter, which becomes active around P15, and activation of GSK-3β is observed at 6–8 weeks. Increased phosphorylation of tau is first observed at 3–4 months of age, although tau does not become aggregated until 7–8 months of age. Memory deficits become first apparent at this time point. Neuronal loss and up-regulation of NPY are not observed up to 12–15 months of age but become apparent >18 months of age. AD-related pathological features described in this study are shown in open ovals.