Comparison of the Amyloid Load in the Brains of Two Transgenic Alzheimer’s Disease Mouse Models Quantified by Florbetaben Positron Emission Tomography

• Main Authors: Antje Willuweit, Michael Schöneck, Sarah Schemmert, Philipp Lohmann, Saskia Bremen, Dominik Honold, Nicole Burda, Nan Jiang, Simone Beer, Johannes Ermert, Dieter Willbold, N. Jon Shah, Karl-Josef Langen
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-10-01
• Series: Frontiers in Neuroscience
• Subjects: Alzheimer’s disease; small animal imaging; florbetaben; amyloid imaging; plaque burden; amyloidosis mouse model
• Online Access: https://www.frontiersin.org/articles/10.3389/fnins.2021.699926/full

Alzheimer’s disease (AD) is characterized by formation of amyloid plaques and neurofibrillary tangles in the brain, which can be mimicked by transgenic mouse models. Here, we report on the characterization of amyloid load in the brains of two transgenic amyloidosis models using positron emission tomography (PET) with florbetaben (FBB), an 18F-labeled amyloid PET tracer routinely used in AD patients. Young, middle-aged, and old homozygous APP/PS1 mice (ARTE10), old hemizygous APPswe/PS1ΔE9, and old wild-type control mice were subjected to FBB PET using a small animal PET/computed tomography scanner. After PET, brains were excised, and ex vivo autoradiography was performed. Plaque pathology was verified on brain sections with histological methods. Amyloid plaque load increased progressively with age in the cortex and hippocampus of ARTE10 mice, which could be detected with both in vivo FBB PET and ex vivo autoradiography. FBB retention showed significant differences to wild-type controls already at 9 months of age by both in vivo and ex vivo analyses. An excellent correlation between data derived from PET and autoradiography could be obtained (rPearson = 0.947, p < 0.0001). Although amyloid load detected by FBB in the brains of old APPswe/PS1ΔE9 mice was as low as values obtained with young ARTE10 mice, statistically significant discrimination to wild-type animals was reached (p < 0.01). In comparison to amyloid burden quantified by histological analysis, FBB retention correlated best with total plaque load and number of congophilic plaques in the brains of both mouse models. In conclusion, the homozygous ARTE10 mouse model showed superior properties over APPswe/PS1ΔE9 mice for FBB small animal amyloid PET imaging. The absolute amount of congophilic dense-cored plaques seems to be the decisive factor for feasibility of amyloidosis models for amyloid PET analysis.