Asymmetry of Fibrillar Plaque Burden in Amyloid Mouse Models
Christian Sacher, Tanja Blume, Leonie Beyer, Gloria Biechele, Julia Sauerbeck, Florian Eckenweber, Maximilian Deußing, Carola Focke, Samira Parhizkar, Simon Lindner, Franz‐Josef Gildehaus, Barbara von Ungern‐Sternberg, Karlheinz Baumann, Sabina Tahirović, Gernot Kleinberger, Michael Willem, Christian Haass, Peter Bartenstein, Paul Cumming, Axel Rominger, Jochen Herms, Matthias Brendel
Abstract
Asymmetries of amyloid- (A) burden are well known in Alzheimer disease (AD) but did not receive attention in A mouse models of Alzheimer disease. Therefore, we investigated A asymmetries in A mouse models examined by A small-animal PET and tested if such asymmetries have an association with microglial activation. Methods: We analyzed 523 cross-sectional A PET scans of 5 different A mouse models (APP/PS1, PS2APP, APP-SL70, App NL-G-F , and APPswe) together with 136 18-kDa translocator protein (TSPO) PET scans for microglial activation. The asymmetry index (AI) was calculated between tracer uptake in both hemispheres. AIs of A PET were analyzed in correlation with TSPO PET AIs. Extrapolated required sample sizes were compared between analyses of single and combined hemispheres. Results: Relevant asymmetries of A deposition were identified in at least 30% of all investigated mice. There was a significant correlation between AIs of A PET and TSPO PET in 4 investigated A mouse models (APP/PS1: R 5 0.593, P 5 0.001; PS2APP: R 5 0.485, P 5 0.019; APP-SL70: R 5 0.410, P 5 0.037; App NL-G-F : R 5 0.385, P 5 0.002). Asymmetry was associated with higher variance of tracer uptake in single hemispheres, leading to higher required sample sizes. Conclusion: Asymmetry of fibrillar plaque neuropathology occurs frequently in A mouse models and acts as a potential confounder in experimental designs. Concomitant asymmetry of microglial activation indicates a neuroinflammatory component to hemispheric predominance of fibrillary amyloidosis.