The leptin system, on the other hand, exhibits bidirectional regulatory features: Conversely, it enhances synaptic plasticity through hippocampal LepRb receptors [304] and improves spatial memory [305]; on the other hand, it inhibits osteoclastogenesis through STAT3 signaling [306], whose deficiency leads to bone metabolism abnormalities and cognitive decline [307], and is independently predictive of AD risk in human [308]. Here, LEP is linked to Alzheimer disease.