期刊
JOURNAL OF NUCLEAR MEDICINE
卷 61, 期 12, 页码 -出版社
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.120.242750
关键词
asymmetry; amyloid; microglia; mouse models
资金
- Koselleck Project of the DFG [HA1737/16-1]
- HelmholtzGemeinschaft (Zukunftsthema Immunology and Inflammation'') [ZT0027]
- Cure Alzheimer's fund
- Deutsche Forschungsgemeinschaft [BR4580/1-1, RO5194/1-1]
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.
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