Among the first pieces of evidence indicating that abnormal Wnt signalling could be involved in AD came from a study that discovered a polymorphism in the GSK3β promoter, which increased its activity and conferred increased susceptibility to LOAD [114] (given the known biological role of GSK-3β, increased activity reduces canonical Wnt signalling by promoting β-catenin degradation). This evidence concerns the gene GSK3B and Alzheimer disease.