Alzheimer’s disease (AD) is a progressive brain disorder resulting in profound cognitive and memory impairments. Clinical studies indicate that diet and lifestyle are key risk factors for developing neurodegenerative disorders like AD. Metabolic imbalance is also implicated in AD. Recent studies have linked the metabolic hormone, leptin to an increased incidence of AD. Consequently, leptin dysfunction may be a key factor in AD pathogenesis. Thus leptin-based therapies may prove beneficial in treating AD. But, leptin treatment per se may not be the best therapeutic approach due to its widespread action in the brain and periphery. However, several bioactive leptin fragments, with differing anti-obesity actions , have been identified. But the cognitive enhancing properties or neuro-protective effects of the leptin fragments are completely unknown. Here we propose to use a multi-disciplinary approach to evaluate the effects of several bio-active leptin fragments in preventing hippocampal synaptic disruption and cell death in cellular models of AD.