In:
Alzheimer's & Dementia, Wiley, Vol. 16, No. S4 ( 2020-12)
Abstract:
Asymmetries of neuropathology, including amyloid‐β (Aβ) burden, are a well‐known phenomenon in patients with Alzheimer’s disease (AD). Yet the occurrence of asymmetric Aβ deposition in amyloid mouse models of AD is scantly documented. Therefore, we first aimed to investigate Aβ‐asymmetries in a comprehensive study of five different amyloid mouse models examined by Aβ‐ small animal positron‐emission‐tomography (PET). Second, we assessed whether any such asymmetries have an association with microglial activation. Method 523 historical cross‐sectional [ 18 F]‐florbetaben Aβ‐PET scans of five different amyloid mouse models ( App NL‐G‐F , APP‐SL70, PS2APP, APP/PS1, and APPswe) and 27 wild‐type mice were analyzed. 136 of these mice (four models) had also undergone contemporaneous [ 18 F]‐GE‐180 18kDa translocator protein (TSPO)‐PET for microglial activation. The asymmetry index (AI) between the left and the right forebrain was calculated for both tracers. AI values outside the 95%/99% confidence intervals of wild‐type mice were defined as having moderate/strong asymmetry. We also analyzed the AI of Aβ‐PET as a function of age and in correlation with TSPO‐PET AI and calculated extrapolated sample sizes required for analyses of single and combined hemispheres. Result Moderate/strong asymmetries of Aβ deposition were identified in 40%/30% of transgenic mice, occurring most frequently in the PS2APP and App NL‐G‐F models (see Figure 1). A significant left dominance in PS2APP and a significant right hemispheric dominance in APPswe mice were observed for Aβ deposition. There was no age dependency of AI, but there was a significant correlation between AIs of Aβ‐PET and TSPO‐PET (all R 〉 0.3, all p 〈 0.05; Figure 2). Asymmetry was associated with higher variance of SUVR in single hemispheres, leading to higher required sample sizes for a given power (see Figure 3). Conclusion Asymmetry of plaque neuropathology occurs frequently in amyloid mouse models of AD, contributing importantly to variance of results in single hemispheres. Concomitant asymmetry of microglial activation indicates a neuroinflammatory component to hemispheric predominance of fibrillary amyloidosis. Important lateralized distribution of fibrillar plaques has likely been a confounding factor in previous studies with Aβ mouse models and is not sufficiently considered.
Type of Medium:
Online Resource
ISSN:
1552-5260
,
1552-5279
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2201940-6
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