Given that altering levels of Shh in skin by constitutive genetic mutation changed disease outcome on AD induction, we next investigated in WT mice, whether systemic inhibition of the Hh signaling pathway would also have a detrimental effect on skin pathology on AD induction, using the PF-04449913 Smo-inhibitor (Smo-inh) (29, 30). The gene discussed is SMO; the disease is Alzheimer disease.