Longitudinal [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-[F]fluoroglucose ([F]FDG)-PET/CT and proton magnetic resonance spectroscopy (H-MRS) served to record neurochemical status.

RESULTS

By using [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 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.