Alzheimer’s disease (AD) is a progressive brain disorder that leads to profound cognitive and memory impairments. The prevalence of AD is predicted to rise rapidly in the future, which will pose a huge burden on health care services in the coming years. Evidence is growing that diet and lifestyle are key risk factors for developing AD and clinical studies indicate that metabolic dysfunction is a common trait in AD.
In addition, low levels of the anti-obesity hormone, leptin have been linked to an increased incidence of AD. Consequently aberrant leptin function is thought to be an important factor in AD pathogenesis. Recent studies in our laboratory support this hypothesis. Indeed, leptin displays cognitive enhancing properties as it markedly enhances the cellular processes that allow the brain to learn and remember information, whereas deficits in the leptin system result in impaired cognitive function. Moreover, treatment with leptin reverses Aβ-induced synaptic dysfunction in rodent models of AD. Thus the endogenous leptin system is a potential novel target for treating AD. Thus to facilitate the design of clinical strategies to potentially prevent or reverse the cognitive deficits in AD, it is critical that the cellular effectors mediating the cognitive enhancing effects of leptin are well defined.
Here we aim to use a multidisciplinary approach to evaluate in detail the role of the leptin system in regulating the early pathological changes in synaptic function in AD. We will also validate the effectiveness of the leptin system as a novel therapeutic target in AD.