Decreased synaptic vesicle glycoprotein 2A binding in a rodent model of familial Alzheimer's disease detected by [18F]SDM-16

Abstract

Introduction: Synapse loss is one of the hallmarks of Alzheimer's disease (AD) and is associated with cognitive decline. In this study, we tested [¹⁸F]SDM-16, a novel metabolically stable SV2A PET imaging probe, in the transgenic APPswe/PS1dE9 (APP/PS1) mouse model of AD and age-matched wild-type (WT) mice at 12 months of age.

Methods: Based on previous preclinical PET imaging studies using [¹¹C]UCB-J and [¹⁸F]SynVesT-1 in the same strain animals, we used the simplified reference tissue model (SRTM), with brain stem as the pseudo reference region to calculate distribution volume ratios (DVRs).

Results: To simplify and streamline the quantitative analysis, we compared the standardized uptake value ratios (SUVRs) from different imaging windows to DVRs and found that the averaged SUVRs from 60-90 min post-injection (p.i.) are most consistent with the DVRs. Thus, we used averaged SUVRs from 60-90 min for group comparisons and found statistically significant differences in the tracer uptake in different brain regions, e.g., hippocampus (p = 0.001), striatum (p = 0.002), thalamus (p = 0.003), and cingulate cortex (p = 0.0003).

Conclusions: In conclusion, [¹⁸F]SDM-16 was used to detect decreased SV2A levels in the brain of APP/PS1 AD mouse model at one year old. Our data suggest that [¹⁸F]SDM-16 has similar statistical power in detecting the synapse loss in APP/PS1 mice as [¹¹C]UCB-J and [¹⁸F]SynVesT-1, albeit later imaging window (60-90 min p.i.) is needed when SUVR is used as a surrogate for DVR for [¹⁸F]SDM-16 due to its slower brain kinetics.

Keywords: APP/PS1; DVR; PET; SRTM; SUVR; SV2A; [18F]SDM-16; brain.