Asymmetry of Fibrillar Plaque Burden in Amyloid Mouse Models.

Sacher, Christian; Blume, Tanja; Beyer, Leonie; Biechele, Gloria; Sauerbeck, Julia; Eckenweber, Florian; Deussing, Maximilian; Focke, Carola; Parhizkar, Samira; Lindner, Simon; Gildehaus, Franz-Josef; von Ungern-Sternberg, Barbara; Baumann, Karlheinz; Tahirovic, Sabina; Kleinberger, Gernot; Willem, Michael; Haass, Christian; Bartenstein, Peter; Cumming, Paul; Rominger, Axel; ... (2020). Asymmetry of Fibrillar Plaque Burden in Amyloid Mouse Models. Journal of nuclear medicine, 61(12), pp. 1825-1831. Society of Nuclear Medicine 10.2967/jnumed.120.242750

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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, 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 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; 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 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.

Keywords: amyloid; asymmetry; microglia; mouse models.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine

UniBE Contributor:

Cumming, Paul and Rominger, Axel Oliver

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0161-5505

Publisher:

Society of Nuclear Medicine

Language:

English

Submitter:

Sabine Lanz

Date Deposited:

04 Jan 2021 08:49

Last Modified:

04 Jan 2021 08:49

Publisher DOI:

10.2967/jnumed.120.242750

PubMed ID:

32414948

Uncontrolled Keywords:

amyloid asymmetry microglia mouse models

BORIS DOI:

10.48350/149165

URI:

https://boris.unibe.ch/id/eprint/149165

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