LEAP2 and Cognitive impairment: It was found that Aβ binds to and inhibits hippocampal GHSR1α activity in 5xFAD mice, resulting in synaptic deficits and cognitive decline.554 In addition, plasma ghrelin levels reduce gradually in 3xTg-AD mice with aging, which is reversed by the administration of multi-strain probiotics formulation (SLAB51), leading to the attenuation of cognitive impairment.555 A recent study in the elderly reported an age-dependent reduction in plasma ghrelin and an elevated ratio of plasma liver-expressed antimicrobial peptide 2 (LEAP2)/ghrelin, which is associated with cognitive impairment.