Among neurodegenerative diseases, Alzheimer disease (AD) is a leading cause of death in elderly individuals. AD is characterized, among other clinical findings, by unexplained weight loss, cachexia and altered immune function. Alteration in energy balance and nutritional status are relayed to the feeding-related hypothalamic nuclei by neuronal pathways and/or via alterations in the levels of eating-controlling hormones. The adipocyte-derived hormone, leptin, and the pancreatic-derived peptide, insulin, function as hormonal signaling mechanisms for fat deposition and play a key role in regulating food intake, body weight and energy homeostasis via their actions on specific hypothalamic nuclei. Moreover, leptin, insulin and their receptors are widely expressed in many hypothalamic and extra-hypothalamic brain regions indicating that these hormones may have other neuronal functions. Although emerging evidence supports the role of insulin resistance in the development of AD, the potential involvement of leptin in the pathogenic process of AD has been proposed only recently. Here we review recent reports and progress concerning the molecular mechanism and the potential role of leptin and insulin in AD.