In this study, we discovered that Amyloid-β, which plays a central role in Alzheimer’s disease pathogenesis, (i) distorts primary cilia structure, (ii) disrupts canonical Sonic hedgehog (Shh) signaling and (iii) that its precursor, APP, localizes to the primary cilium along with smoothened (Smo) a known cilia resident Shh signaling component. The gene discussed is SMO; the disease is early-onset autosomal dominant Alzheimer disease.