Although extracellular CPE no longer exhibits enzymatic activity at pH conditions around 7.0–7.3 thus failing to process proBDNF, it may function as a neuroprotective factor to ameliorate the AD-linked pathologies by interacting with human serotonin receptor HTR1E to activate the ERK–CREB signaling pathway, leading to the upregulation of mitochondrial prosurvival protein BCL2 [56]. Here, CREB1 is linked to Alzheimer disease.