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

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.

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-[¹⁸F]fluoroglucose ([¹⁸F]FDG)-PET/CT and proton magnetic resonance spectroscopy (¹H-MRS) served to record neurochemical status.

By using [¹⁸F]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 ¹H-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.

In summary, this longitudinal in vivo study shows for the first time that ApoE-/- mice depict cerebral hypometabolism without neurochemical alterations.