In our previous study, we have shown that Shh expression was enhanced in the cortex and hippocampus of the aged (12-month-old) brains of APPswe/PSEN1dE9 mice, a commonly used AD transgenic mouse model, as compared to the wild-type littermates; interestingly, the expression of Shh also progressively elevated in the wild-type brains during aging, from 3 to 12 months of age [32]. Here, SHH is linked to Alzheimer disease.