Asymmetries of amyloid-β (Aβ) burden are well known in Alzheimer disease (AD) but did not receive attention in Aβ mouse models of Alzheimer disease. Therefore, we investigated Aβ asymmetries in Aβ mouse models examined by Aβ small-animal PET and tested if such asymmetries have an association with microglial activation. Methods: We analyzed 523 cross-sectional Aβ PET scans of 5 different Aβ 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 Aβ 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 Aβ deposition were identified in at least 30% of all investigated mice. There was a significant correlation between AIs of Aβ PET and TSPO PET in 4 investigated Aβ mouse models (APP/PS1: R = 0.593, P = 0.001; PS2APP: R = 0.485, P = 0.019; APP-SL70: R = 0.410, P = 0.037; App NL-G-F : R = 0.385, P = 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 Aβ 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.
Asymmetries of amyloid-β (Aβ) burden are well known in Alzheimer disease (AD) but did not receive attention in Aβ mouse models of Alzheimer disease. Therefore, we investigated Aβ asymmetries in Aβ mouse models examined by Aβ small-animal PET and tested if such asymmetries have an association with microglial activation. Methods: We analyzed 523 cross-sectional Aβ PET scans of 5 different Aβ 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 Aβ 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 Aβ deposition were identified in at least 30% of all investigated mice. There was a significant correlation between AIs of Aβ PET and TSPO PET in 4 investigated Aβ mouse models (APP/PS1: R = 0.593, P = 0.001; PS2APP: R = 0.485, P = 0.019; APP-SL70: R = 0.410, P = 0.037; App NL-G-F : R = 0.385, P = 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 Aβ 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.
Authors: Ruiqing Ni; Zhenyue Chen; Xosé Luís Deán-Ben; Fabian F Voigt; Daniel Kirschenbaum; Gloria Shi; Alessia Villois; Quanyu Zhou; Alessandro Crimi; Paolo Arosio; Roger M Nitsch; K Peter R Nilsson; Adriano Aguzzi; Fritjof Helmchen; Jan Klohs; Daniel Razansky Journal: Nat Biomed Eng Date: 2022-07-14 Impact factor: 29.234
Authors: Gloria Biechele; Nicolai Franzmeier; Tanja Blume; Michael Ewers; Jose Medina Luque; Florian Eckenweber; Christian Sacher; Leonie Beyer; Francois Ruch-Rubinstein; Simon Lindner; Franz-Josef Gildehaus; Barbara von Ungern-Sternberg; Paul Cumming; Peter Bartenstein; Axel Rominger; Günter U Höglinger; Jochen Herms; Matthias Brendel Journal: J Neuroinflammation Date: 2020-12-14 Impact factor: 8.322
Authors: Gloria Biechele; Laura Sebastian Monasor; Karin Wind; Tanja Blume; Samira Parhizkar; Thomas Arzberger; Christian Sacher; Leonie Beyer; Florian Eckenweber; Franz-Josef Gildehaus; Barbara von Ungern-Sternberg; Michael Willem; Peter Bartenstein; Paul Cumming; Axel Rominger; Jochen Herms; Stefan F Lichtenthaler; Christian Haass; Sabina Tahirovic; Matthias Brendel Journal: J Nucl Med Date: 2021-05-20 Impact factor: 11.082