Food for thought: Leptin regulation of hippocampal function and its role in Alzheimer's disease

Abstract

Accumulating evidence indicates that diet and body weight are important factors associated with Alzheimer's disease (AD), with a significant increase in AD risk linked to mid-life obesity, and weight loss frequently occurring in the early stages of AD. This has fuelled interest in the hormone leptin, as it is an important hypothalamic regulator of food intake and body weight, but leptin also markedly influences the functioning of the hippocampus; a key brain region that degenerates in AD. Increasing evidence indicates that leptin has cognitive enhancing properties as it facilitates the cellular events that underlie hippocampal-dependent learning and memory. However, significant reductions in leptin's capacity to regulate hippocampal synaptic function occurs with age and dysfunctions in the leptin system are associated with an increased risk of AD. Moreover, leptin is a potential novel target in AD as leptin treatment has beneficial effects in various models of AD. Here we summarise recent advances in leptin neurobiology with particular focus on regulation of hippocampal synaptic function by leptin and the implications of this for neurodegenerative disorders like AD.This article is part of the Special Issue entitled ‘Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.’