HIF1A and Alzheimer disease: Hypoxia caused increased Aβ deposition in AD mouse models [137–139] and this effect was shown, both in cells and in AD mouse models, to be regulated by an increase in γ-secretase activity resulting from the direct interaction of γ-secretase with hypoxic-inducible factor 1-α (HIF-1α) [140], or via the demethylation of the gene encoding γ-secretase [141].