APP and Alzheimer disease: Therefore, it is not surprising that hypoxia significantly increases the risk of developing neurodegenerative diseases, in particular AD, with the dysregulation of the HIF-1α pathway leading to AβPP amyloidogenic processing with Aβ accumulation, due to increased production [207,208,209] and/or decreased degradation [210], tau hyperphosphorylation and microglial activation [211].