Leptin: The Missing Link in Alzheimer Disease?

Abstract

In Western societies, life expectancy is increasing steadily. As a consequence, more individuals are suffering from age-related disorders such as Alzheimer disease (AD).1 The prevalence of AD is predicted to rise rapidly in the coming decades, which is likely to pose a huge burden on healthcare services in the future. Although significant advances have been made in this field in recent years, our understanding of the principle cellular changes that occur in the initial stages of this disease and the means to identify these changes clinically are limited. Thus key research priorities are to determine the key cellular events that underlie the development and pathogenesis of AD and identify possible biomarkers associated with the early stages of AD. Studies in these areas are of paramount importance, as they are likely to aid in the detection of the early brain changes in AD and could potentially lead to the development of novel therapies to treat this debilitating neurodegenerative disorder. Combinations of factors, such as lifestyle, genetic, and vascular influences, are known to modify the risk of developing AD. Several lines of evidence also support a link between midlife obesity and an increased risk of AD, but the mechanisms responsible for this association are not entirely clear. Recent studies have identified the endocrine hormone leptin as a possible factor linking obesity and AD. Leptin plays a pivotal role in the regulation of food intake and body weight via its actions on specific nuclei within the hypothalamus. In addition, leptin receptors are expressed in many extrahypothalamic brain regions, and numerous studies indicate that leptin is a pleiotropic hormone with diverse actions reported throughout the central nervous system (CNS). In particular, limbic structures such as the hippocampus display high levels …