RT Journal Article
SR Electronic
T1 Asymmetry of Fibrillar Plaque Burden in Amyloid Mouse Models
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1825
OP 1831
DO 10.2967/jnumed.120.242750
VO 61
IS 12
A1 Christian Sacher
A1 Tanja Blume
A1 Leonie Beyer
A1 Gloria Biechele
A1 Julia Sauerbeck
A1 Florian Eckenweber
A1 Maximilian Deussing
A1 Carola Focke
A1 Samira Parhizkar
A1 Simon Lindner
A1 Franz-Josef Gildehaus
A1 Barbara von Ungern-Sternberg
A1 Karlheinz Baumann
A1 Sabina Tahirovic
A1 Gernot Kleinberger
A1 Michael Willem
A1 Christian Haass
A1 Peter Bartenstein
A1 Paul Cumming
A1 Axel Rominger
A1 Jochen Herms
A1 Matthias Brendel
YR 2020
UL http://jnm.snmjournals.org/content/61/12/1825.abstract
AB Asymmetries of amyloid-β (Aβ) burden are well known in Alzheimer disease (AD) but did not receive attention in Aβ mouse models of Alzheimer disease. Therefore, we investigated Aβ asymmetries in Aβ mouse models examined by Aβ small-animal PET and tested if such asymmetries have an association with microglial activation. Methods: We analyzed 523 cross-sectional Aβ PET scans of 5 different Aβ mouse models (APP/PS1, PS2APP, APP-SL70, AppNL-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 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 at least 30% of all investigated mice. There was a significant correlation between AIs of Aβ PET and TSPO PET in 4 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.