They propose that amyloid-beta (Aβ), a key protein in the senile plaques of AD, may down-regulate the Wnt/β-catenin pathway, thereby upregulating GSK3β and its subsequent hyperphosphorylation of tau, linking Aβ and the neurofibrillary pathology characteristic of AD and ALS-PDC. This evidence concerns the gene GSK3B and Alzheimer disease.