Debby Van Dam, Belgium
Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge Department of Biomedical Sciences, University of AntwerpAuthor Of 1 Presentation
TRANSIENT PERIPHERAL INSULIN RESISTANCE IN A MUTATED HAPP OVEREXPRESSING MOUSE MODEL OF ALZHEIMER’S DISEASE
Abstract
Aims
Increasing epidemiological evidence highlighted the correlation between central metabolic dysfunction, such as insulin resistance, and Alzheimer’s disease (AD). In the present study, we aimed to investigate the systemic metabolic phenotype in a mutated hAPP overexpressing mouse model of AD (APP23+/-) with a specific focus on the systemic insulin functionality.
Methods
Age-matched APP23+/- and C57BL/6 J mice at 4 (n=7-11) and 12 months (n=11-21) were tested for memory and spatial learning by a Morris Water Maze (MWM) test. In addition, animals were metabolically tested with an intraperitoneal glucose and insulin tolerance test (GTT, ITT). Circulating insulin levels were determined in blood serum. Data are represented as mean ± SEM.
Results
MWM data revealed cognitive decline in APP23+/- at 12 months of age, as total path lengths increased compared to C57BL/6 animals (AUC= 129 ± 8 vs. 172 ± 2 m; p=0.0003). Peripheral glucose homeostasis remained unchanged. At 4 months of age, APP23+/- mice presented with peripheral insulin resistance compared to control littermates (AUC= 984 ± 272 vs. 2007 ± 238 mg*min/dL; p=0.007), which stabilized at 12 months of age. Serum insulin levels were similar between genotypes at 4 months (0.6 ± 0.1 and 0.4 ± 0.1 ng/mL, respectively), but were significantly elevated in APP23+/- mice (1.9 ± 0.9 vs. 1.1 ± 0.1 ng/mL; p=0.002) at 12 months of age.
Conclusions
These results suggest that peripheral insulin resistance could be a potential metabolic biomarker in the pre-symptomatic phase of AD.