Asymmetry of plaque burden in amyloid mouse models

Ziel/Aim Asymmetries of neuropathology, including amyloid-β (Aβ) burden, in patients of Alzheimer’s disease (AD) are a well-known phenomenon. Yet, there is less evidence, how frequent Aβ-asymmetries occur in different amyloid mouse models of AD.Therefore, we aimed to assess Aβ-asymmetries in five different amyloid mouse models by terms of Aβ- small animal positron-emission-tomography (PET). Second, we assessed whether observed asymmetries are associated with microglial activation.

Methodik/Methods 523 cross-sectional ¹⁸F-florbetaben PETscans of App^NL-G-F(n = 55; age: 2.5-10 months), APP-SL70 (n = 208; age: 4-15 months), PS2APP (n = 147; age: 6-17 months), APP/PS1 (n = 41; age: 3-12 months) and APPswe (n=72; age: 9-20 months) mice were analyzed. C57BI/6 mice (n = 27 scans age: 2.5-16 months) served as controls (WT). App^NL-G-F(n = 55), APP-SL70 (n = 26), PS2APP (n = 23) and APP/PS1 (n = 27) mice had also received a contemporaneous ¹⁸F-GE-180 18kDa translocator protein (TSPO)-PET for microglial activation. The asymmetry index (AI) between the left and the right forebrain (cortex and hippocampus) was calculated. To account for unspecific asymmetric tracer distribution, only values outside the 95 %/99 % confidence interval of WT-AI were defined as moderate/strong asymmetric. AI of ¹⁸F-florbetaben PETwere analyzed as a function of age and in correlation with ¹⁸F-GE-180 PET AI.

Ergebnisse/Results Moderate/strong asymmetries of Aβ deposition were identified in 40 %/30 % of transgenic mice. Most frequent asymmetries were observed in PS2APP (49 %/37 %) and App^NL-G-F (49 %) and mice. Age dependency of asymmetry was not discernable. AI of ¹⁸F-florbetaben Aβ-PET and ¹⁸F-GE-180 TSPO-PET were significantly associated (all R > 0.4) in four investigated amyloid mouse models.

Schlussfolgerungen/Conclusions Asymmetry of plaque neuropathology is frequent in amyloid mouse models and needs attention when single hemispheres are investigated by ex vivomethods. Asymmetries of microglial activation occur concomitant in the hemisphere with predominant fibrillary amyloidosis.