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.
Item Type: | Journal article |
---|---|
Faculties: | Medicine Medicine > Munich Cluster for Systems Neurology (SyNergy) |
Subjects: | 600 Technology > 610 Medicine and health |
URN: | urn:nbn:de:bvb:19-epub-87349-8 |
ISSN: | 0161-5505 |
Language: | English |
Item ID: | 87349 |
Date Deposited: | 25. Jan 2022, 09:23 |
Last Modified: | 02. Aug 2024, 12:32 |
DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |