Longitudinal [ 18 F]FDG-PET/CT analysis of the glucose metabolism in ApoE -deficient mice

Background Strong line of evidence suggests that the increased risk to develop AD may at least be partly mediated by cholesterol metabolism. A key regulator of cholesterol transport is the Apolipoprotein E4 (ApoE4), which plays a fundamental role in neuronal maintenance and repair. Impaired function of ApoE4 may contribute to altered cerebral metabolism leading to higher susceptibility to neurodegeneration. Methods To determine a possible link between ApoE function and alterations in AD in the brain of Apolipoprotein E-deficient mice ( ApoE −/−) in a longitudinal manner metabolic and neurochemical parameters were analyzed. Cortical metabolism was measured by 2-deoxy-2-[ 18 F]fluoroglucose ([ 18 F]FDG)-PET/CT and proton magnetic resonance spectroscopy ( 1 H-MRS) served to record neurochemical status. Results By using [ 18 F]FDG-PET/CT, we showed that brain metabolism declined significantly stronger with age in ApoE −/− versus wild type (wt) mice. This difference was particularly evident at the age of 41 weeks in almost each analyzed brain region. In contrast, the 1 H-MRS-measured N -acetylaspartate to creatine ratio, a marker of neuronal viability, did not decline with age and did not differ between ApoE −/− and wt mice. Conclusion In summary, this longitudinal in vivo study shows for the first time that ApoE −/− mice depict cerebral hypometabolism without neurochemical alterations.