PSEN1 and neurodegenerative disease: In contrast, the individual roles of β-catenin and PS-1 in neurodegenerative disease together with their coordinate dysregulation by knockdown of the housekeeping gene HPRT suggest that aberrant Wnt and PS-1 pathways may interact and cooperate to produce pathogenic components that individually are subtle but that in the aggregate produce powerfully disrupting effects on vital neural pathways, such as those seen in human HPRT deficiency.