APP and Mental deterioration: Considering that recent studies performed in the central nervous system highlight the pathophysiological relevance of hypoxia/HIF-1 pathways regulation of β-secretase 1 (BACE1) expression and amyloid precursor protein (APP) amyloidogenic metabolism (Zhang et al., 2007; Bulbarelli et al., 2012), alterations in HIF-1α protein levels/degradation pathway may contribute to the cognitive decline and dementia in AD patients influencing the disease course.