Metabolic changes over the course of aging in a mouse model of tau deposition.

Weight loss and food intake disturbances that often precede cognitive decline and diagnosis have been extensively reported in Alzheimer's disease patients. Previously, we observed that transgenic mice overexpressing tau seemed to eat more food yet weigh less than nontransgenic littermates. Thus, the present longitudinal study measured the time course of changes in metabolic state over the lifespan of the tau depositing Tg4510 mouse model of tau deposition. Although body weight was comparable to nontransgenic littermates at 2 months of age, Tg4510 mice weighed less at older ages. This was accompanied by the accumulation of tau pathology and by dramatically increased activity in all phases of the 24-hour cycle. Resting metabolic rate was also increased at 7 months of age. At 12 months near the end of the Tg4510 lifespan, there was a wasting phase, with a considerable decrease of resting metabolic rate, although hyperactivity was maintained. These diverse changes in metabolism in a mouse model of tau deposition are discussed in the context of known changes in energy metabolism in Alzheimer's disease.