SHH and early-onset autosomal dominant Alzheimer disease: Multiple studies showed the beneficial role of Shh signaling in various models of neurological conditions, including stroke,10,13, 14, 15, 16, 17, 18 acute brain injury,19 Parkinson's disease,20,21 Alzheimer's disease,22 multiple sclerosis and demyelination,11,23,24 spinal cord injury,25,26 amyotrophic lateral sclerosis,27 and glucocorticoid-induced cerebellar injury in neonates.28 However, the potential of pharmacological activation of Shh signaling in injured CNS and associated neuroprotective mechanisms are unknown.