Abstract
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Objectives We aimed to investigate the progression of amyloid-β deposition in brain of mice over-expressing amyloid-precursor protein (APP-Swe), a model of Alzheimer’s disease (AD), in a longitudinal PET study with the novel amyloid-β tracer [18F]florbetaben.
Methods Groups of APP-Swe mice (N=8) and age-matched WT mice (N=8) were investigated at the ages of 10, 13 and 16 months (48 scans). Dynamic emission recordings were acquired with the Inveon microPET during 90 minutes following administration of [18F]florbetaben. After spatial normalization of individual PET recordings to a common coordinate system for mouse brain, cortex-to-cerebellum ratios (CCR) were calculated using a region-of-interest (ROI) approach. Furthermore voxel-wise analyses were performed using statistical parametric mapping (SPM). Immunohistochemical analyses and ex vivo autoradiography were performed in a subset of animals as a gold standard assessment of amyloid plaque load.
Results At the age of 10 months CCR was 0.97±0.06 in WT and 1.00±0.04 (p=n.s.) in APP-Swe mice. At the age of 13 months APP-Swe mice showed a significant 9.5% increase (p < 0.001) in cortical [18F]florbetaben uptake compared to that seen at 10 months, and at 16 months there was a 20.0% increase compared to baseline (p < 0.0001), whereas WT mice did not show any temporal changes in cortical binding during the interval of follow-up. SPM analyses revealed progressive binding increases in frontal as well as temporal cortex (p<0.001 uncorr).
Conclusions This is the first longitudinal study in an AD mouse model using the novel fluorinated β-amyloid tracer [18F]florbetaben. We were able to monitor sensitively the temporal and spatial progression of amyloidogenesis in the brain of APP-Swe mice. We predict that this method should afford the means for preclinical testing of novel therapeutic approaches to the treatment of AD.
Research Support Florbetaben was provided by Bayer Schering