NFE2L2 and Cognitive impairment: Moreover, this pathway appears to be activated in chronic disease as well: the Nrf2 target gene NQO1 is upregulated in plaque-surrounding astrocytes in human AD post-mortem samples, but not in areas unaffected by pathology [83] and HMOX1 was found to be elevated in temporal cortex and hippocampus in patients with both AD and mild cognitive impairment [84], with elevation in early disease suggesting that Nrf2 activation occurs relatively early in human neurodegenerative processes rather than representing an end-stage process.