The requirement for microglial activation in the P4-E2 antagonism of neurite outgrowth further suggests that microglial activation, such as arises during aging and Alzheimer disease, might alter the absence of P4-E2 antagonism in regulation of hippocampal neuron Pgrmc1 in vivo (Bali et al., 2012). This evidence concerns the gene PGRMC1 and Alzheimer disease.