Weight loss is common in Alzheimer’s disease (AD) and is predictive of mortality. Leptin, an adipocyte-derived peptide hormone is implicated in the regulation of satiety and energy expenditure. It acts on the hypothalamus to suppress appetite and increase energy expenditure. We undertook this study to determine if inappropriately elevated leptin levels play a role in AD-associated weight loss. Serum leptin levels of 8 patients in each of the following groups were determined: (1) AD, body mass index (BMI) >25; (2) AD, BMI <20; (3) non-Alzheimer’s (vascular) dementia (VaD), BMI >25, and (4) VaD, BMI <20. Mean serum leptin levels were significantly lower in below-appropriate-weight patients (both AD and VaD) than in appropriate-weight controls. Below-appropriate-weight AD patients had a significantly lower mean serum leptin concentration than appropriate-weight VaD controls. Weight loss is a feature of AD. Inappropriately elevated leptin levels do not appear to be implicated. Indeed, we have shown that the afferent limb of the leptin feedback loop is intact in below-appropriate-weight AD patients and suggest hypothalamic dysfunction may underlie this feature.