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Radioligand imaging is a powerful  in vivo  method to assess the molecular basis of Alzheimer’s Disease. We therefore aimed to visualize the pathological deposition of fibrillar amyloid-β and neuronal dysfunction in aged double transgenic mice.    Methods  Using non-invasive positron emission tomography (PET) we assessed brain glucose utilization with [ 18 F]FDG and fibrillar amyloidosis with [ 11 C]PiB and [ 18 F]AV45 in 12 month old APPPS1-21 ( n  = 10) mice and their age-matched wild-type controls ( n  = 15). PET scans were analyzed with statistical parametric mapping (SPM) to detect significant differences in tracer uptake between genotypes. After imaging, mice were sacrificed and  ex vivo  measures of amyloid-β burden with immunohistochemistry as well as glucose utilization with [ 14 C]-2DG autoradiography were obtained as gold standards.    Results  Voxel-wise SPM analysis revealed significantly decreased [ 18 F]FDG uptake in aged APPPS1-21 mice in comparison to WT with the thalamus (96.96 %, maxT = 3.35) and striatum (61.21 %, maxT = 3.29) demonstrating the most widespread reductions at the threshold of  p  < 0.01. [ 11 C]PiB binding was significantly increased in APPPS1-21 mice, most notably in the hippocampus (87.84 %, maxT = 7.15) and cortex (69.08 %, maxT = 7.95), as detected by SPM voxel-wise analysis at the threshold of  p  < 0.01. Using the same threshold [ 18 F]AV45 uptake was comparably lower with less significant differences. Compared to their respective  ex vivo  equivalents [ 18 F]FDG demonstrated significant positive correlation to [ 14 C]2-DG autoradiography (r = 0.67,  p  <0.0001) while [ 11 C]PiB and [ 18 F]AV45 binding did not correlate to  ex vivo  immunohistochemistry for amyloid-β (r = 0.25,  p  = 0.07 and r = 0.17,  p  = 0.26 respectively). Lastly no correlation was observed between regions of high amyloid burden and those with decreased glucose utilization (r = 0.001,  p  = 0.99).    Conclusions  Our findings support that fibrillar amyloid-β deposition and reduced glucose utilization can be visualized and quantified with  in vivo  μPET imaging in aged APPPS1-21 mice. Therefore, the combined use of [ 18 F]FDG and amyloid μPET imaging can shed light on the underlying relationship between fibrillar amyloid-β pathology and neuronal dysfunction.

In vivo molecular neuroimaging of glucose utilization and its association with fibrillar amyloid-β load in aged APPPS1-21 mice