APP and Alzheimer disease: In a transgenic mouse model that overexpresses the human APP (hAPP), increased levels of enkephalins have been found in the hippocampus and entorhinal cortex which are associated with neuronal and cognitive impairments.28 In addition in an APP/PS transgenic mouse model of AD, evidence reported in knockdown or antagonism of the delta opioid receptor has revealed reductions in Aβ accumulation, plaque formation and associated gliosis, and behavioural deficits, a result that supports the role of opioid peptides in Aβ generation.44