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Asymmetry of fibrillar plaque burden in amyloid mouse models.

J Nucl Med. 2020;jnumed.120.242750. doi:10.2967/jnumed.120.242750 [published online ahead of print, 2020 May 15].

Authors/Editors: Sacher C, Blume T, Beyer L, Biechele G, Sauerbeck J, Eckenweber F, Deussing M, Focke C, Parhizkar S, Lindner S, Gildehaus FJ, von Ungern-Sternberg B, Baumann K, Tahirovic S, Kleinberger G, Willem M, Haass C, Bartenstein P, Cumming P, Rominger A, Herms J, Brendel M.
Publication Date: 2020



Objective: Asymmetries of amyloid-β (Aβ) burden, are well-known in Alzheimer's disease (AD), but did not receive attention in Aβ mouse models of AD. Therefore, we investigated Aβ-asymmetries in Aβ mouse models examined by Aβ- small animal positron-emission-tomography (PET) and tested if such asymmetries have an association with microglial activation.

Methods: 523 cross-sectional Aβ-PET scans of five different Aβ mouse models (APP/PS1, PS2APP, APP-SL70, AppNL-G-F and APPswe) were analyzed together with 136 18kDa 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 ≥30% of all investigated mice. There was a significant correlation between AIs of Aβ-PET and TSPO-PET in four 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; AppNL-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.

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