LEP and Alzheimer disease: Intriguingly, leptin concentrations were associated with a reduced incidence of AD in old adults (Lieb et al., 2009), while replacement therapy in genetically leptin deficient humans was accompanied by increases in regional gray matter volume (Matochik et al., 2005; Paz-Filho et al., 2008; London et al., 2011) and improvement in cognitive abilities, further emphasizing the importance of leptin in terms of neuroplasticity and brain function.