P1-074: Eating & drinking in an APP hyperexpression model

Abstract

To model Alzheimer dementia, transgenic mice overexpressing the human amyloid precursor protein encoding the Swedish double mutation were generated. This APP23 model develops pathological features and models the demented patients' learning and memory deficits. We have reported these transgenic mice to exhibit cage activity disturbances, reminiscent of diurnal rhythm disturbances in Alzheimer patients, indicating as well the presence of neuropsychiatric symptoms of dementia. With the aim of verifying whether the model also develops other behavioural problems, we assessed detailed eating and drinking patterns in heterozygous APP23 males of 3, 6 and 12 months of age. Furthermore, we longitudinally monitored body weight of a naive group of males starting at weaning. Eating and drinking behavior were simultaneously recorded by employing Skinner boxes during a 1–week recording period. The mouse cubicles are placed inside ventilated isolation compartments and equipped with a pellet feeder and an optical lickometer. The animals included in the growth curves were weighed twice a week until the age of 12 weeks, with subsequent monthly follow up. We found heterozygous APP23 mice to take a higher number of food pellets and perform significantly more licking responses as well, in comparison with their wild–type littermates. From the age of 4.5 weeks onwards, heterozygous males weighed significantly less and this difference became even more outspoken with increasing age. Demented patients also exhibit weight loss and often dietary problems. Weight loss could induce secondary metabolic alterations which might influence blood flow and cerebral function. Our results seem to support the hypothesis of the existence of a hypermetabolic state in Alzheimer patients. This is the first report, evidencing the existence of changes in eating and drinking behaviour in an Alzheimer mouse model. APP23 mice become an even more promising and valuable animal model for Alzheimer's disease–related research and opens perspectives for pharmacological and/or behavioural interventions.