Hypermetabolism in a triple-transgenic mouse model of Alzheimer's disease

A common feature of Alzheimer's disease (AD) is weight loss, even though there is often an increase in food intake in AD patients. The reasons for this weight loss are unknown, but may be due to increased energy expenditure (metabolic rate) or a reduction in energy intake. This was investigated in the present study, using a triple-transgenic (3xTgAD) mouse model of AD. Two-month-old 3xTgAD mice displayed greater food intake (17%) and body weight (34%) but no difference in metabolic rate, as compared with nontransgenic controls (non-Tg). At 12 months of age, 3xTgAD mice still consumed more food (30%), but their body weight was significantly lower (15%) than non-Tg controls. This reduction in body weight was accompanied by a significant rise in metabolic rate, indicated by greater oxygen consumption (24%) and carbon dioxide production (29%); the effects were also observed in 18-month-old 3xTgAD mice. These data demonstrate for the first time the existence of a hypermetabolic state in an experimental model of AD, but whether this can explain the weight loss observed in AD patients remains to be determined.