Willuweit, Antje, Schoeneck, Michael, Schemmert, Sarah, Lohmann, Philipp ORCID: 0000-0002-5360-046X, Bremen, Saskia, Honold, Dominik, Burda, Nicole, Jiang, Nan, Beer, Simone ORCID: 0000-0003-4290-4051, Ermert, Johannes, Willbold, Dieter, Shah, N. Jon and Langen, Karl-Josef (2021). Comparison of the Amyloid Load in the Brains of Two Transgenic Alzheimer's Disease Mouse Models Quantified by Florbetaben Positron Emission Tomography. Front. Neurosci., 15. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1662-453X

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Abstract

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 F-18-labeled amyloid PET tracer routinely used in AD patients. Young, middle-aged, and old homozygous APP/PS1 mice (ARTE10), old hemizygous APPswe/PS1 Delta E9, 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 (r(Pearson) = 0.947, p < 0.0001). Although amyloid load detected by FBB in the brains of old APPswe/PS1 Delta E9 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/PS1 Delta E9 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Willuweit, AntjeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoeneck, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schemmert, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lohmann, PhilippUNSPECIFIEDorcid.org/0000-0002-5360-046XUNSPECIFIED
Bremen, SaskiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Honold, DominikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burda, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jiang, NanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beer, SimoneUNSPECIFIEDorcid.org/0000-0003-4290-4051UNSPECIFIED
Ermert, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Willbold, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shah, N. JonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langen, Karl-JosefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-590685
DOI: 10.3389/fnins.2021.699926
Journal or Publication Title: Front. Neurosci.
Volume: 15
Date: 2021
Publisher: FRONTIERS MEDIA SA
Place of Publication: LAUSANNE
ISSN: 1662-453X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
COTTON WOOL PLAQUES; IN-VIVO; COMPOUND B; BETA; PET; HETEROGENEITY; DEPOSITION; DEMENTIAMultiple languages
NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59068

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