Asymmetry of Fibrillar Plaque Burden in Amyloid Mouse Models

Sacher, Christian; Blume, Tanja; Beyer, Leonie; Biechele, Gloria; Sauerbeck, Julia; Eckenweber, Florian; Deussing, Maximilian; Focke, Carola; Parhizkar, Samira; Lindner, Simon; Gildehaus, Franz-Josef; Ungern-Sternberg, Barbara von; Baumann, Karlheinz; Tahirovic, Sabina; Kleinberger, Gernot; Willem, Michael; Haass, Christian; Bartenstein, Peter; Cumming, Paul; Rominger, Axel; Herms, Jochen und Brendel, Matthias (2020): Asymmetry of Fibrillar Plaque Burden in Amyloid Mouse Models. In: Journal of Nuclear Medicine, Bd. 61, Nr. 12

Abstract

Asymmetries of amyloid-beta (A beta) burden are well known in Alzheimer disease (AD) but did not receive attention in A beta mouse models of Alzheimer disease. Therefore, we investigated A beta asymmetries in A beta mouse models examined by A beta small-animal PET and tested if such asymmetries have an association with microglial activation. Methods: We analyzed 523 cross-sectional A beta PET scans of 5 different A beta 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 beta 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 beta deposition were identified in at least 30% of all investigated mice. There was a significant correlation between AIs of A beta PET and TSPO PET in 4 investigated AP 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 A beta 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0161-5505
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198