Quantitative Brain Positron Emission Tomography in Female 5XFAD Alzheimer Mice: Pathological Features and Sex-Specific Alterations

Successful back-translating clinical biomarkers and molecular imaging methods of Alzheimer's disease (AD), including positron emission tomography (PET), are very valuable for the evaluation of new therapeutic strategies and increase the quality of preclinical studies. 18F-Fluorodeoxyglucose (FD...

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Autores principales: Caroline Bouter, Caroline Irwin, Timon N. Franke, Nicola Beindorff, Yvonne Bouter
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:55813cdb89144d8a9fe5d94d8bb4ad802021-12-01T06:42:55ZQuantitative Brain Positron Emission Tomography in Female 5XFAD Alzheimer Mice: Pathological Features and Sex-Specific Alterations2296-858X10.3389/fmed.2021.745064https://doaj.org/article/55813cdb89144d8a9fe5d94d8bb4ad802021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmed.2021.745064/fullhttps://doaj.org/toc/2296-858XSuccessful back-translating clinical biomarkers and molecular imaging methods of Alzheimer's disease (AD), including positron emission tomography (PET), are very valuable for the evaluation of new therapeutic strategies and increase the quality of preclinical studies. 18F-Fluorodeoxyglucose (FDG)–PET and 18F-Florbetaben–PET are clinically established biomarkers capturing two key pathological features of AD. However, the suitability of 18F-FDG– and amyloid–PET in the widely used 5XFAD mouse model of AD is still unclear. Furthermore, only data on male 5XFAD mice have been published so far, whereas studies in female mice and possible sex differences in 18F-FDG and 18F-Florbetaben uptake are missing. The aim of this study was to evaluate the suitability of 18F-FDG– and 18F-Florbetaben–PET in 7-month-old female 5XFAD and to assess possible sex differences between male and female 5XFAD mice. We could demonstrate that female 5XFAD mice showed a significant reduction in brain glucose metabolism and increased cerebral amyloid deposition compared with wild type animals, in accordance with the pathology seen in AD patients. Furthermore, we showed for the first time that the hypometabolism in 5XFAD mice is gender-dependent and more pronounced in female mice. Therefore, these results support the feasibility of small animal PET imaging with 18F-FDG- and 18F-Florbetaben in 5XFAD mice in both, male and female animals. Moreover, our findings highlight the need to account for sex differences in studies working with 5XFAD mice.Caroline BouterCaroline IrwinTimon N. FrankeNicola BeindorffYvonne BouterFrontiers Media S.A.article5XFAD Alzheimer modelAlzheimer's diseasepositron - emission tomography18F-Flourdesoxyglucose-PET18F-Florbetaben-PETMedicine (General)R5-920ENFrontiers in Medicine, Vol 8 (2021)
institution DOAJ
collection DOAJ
language EN
topic 5XFAD Alzheimer model
Alzheimer's disease
positron - emission tomography
18F-Flourdesoxyglucose-PET
18F-Florbetaben-PET
Medicine (General)
R5-920
spellingShingle 5XFAD Alzheimer model
Alzheimer's disease
positron - emission tomography
18F-Flourdesoxyglucose-PET
18F-Florbetaben-PET
Medicine (General)
R5-920
Caroline Bouter
Caroline Irwin
Timon N. Franke
Nicola Beindorff
Yvonne Bouter
Quantitative Brain Positron Emission Tomography in Female 5XFAD Alzheimer Mice: Pathological Features and Sex-Specific Alterations
description Successful back-translating clinical biomarkers and molecular imaging methods of Alzheimer's disease (AD), including positron emission tomography (PET), are very valuable for the evaluation of new therapeutic strategies and increase the quality of preclinical studies. 18F-Fluorodeoxyglucose (FDG)–PET and 18F-Florbetaben–PET are clinically established biomarkers capturing two key pathological features of AD. However, the suitability of 18F-FDG– and amyloid–PET in the widely used 5XFAD mouse model of AD is still unclear. Furthermore, only data on male 5XFAD mice have been published so far, whereas studies in female mice and possible sex differences in 18F-FDG and 18F-Florbetaben uptake are missing. The aim of this study was to evaluate the suitability of 18F-FDG– and 18F-Florbetaben–PET in 7-month-old female 5XFAD and to assess possible sex differences between male and female 5XFAD mice. We could demonstrate that female 5XFAD mice showed a significant reduction in brain glucose metabolism and increased cerebral amyloid deposition compared with wild type animals, in accordance with the pathology seen in AD patients. Furthermore, we showed for the first time that the hypometabolism in 5XFAD mice is gender-dependent and more pronounced in female mice. Therefore, these results support the feasibility of small animal PET imaging with 18F-FDG- and 18F-Florbetaben in 5XFAD mice in both, male and female animals. Moreover, our findings highlight the need to account for sex differences in studies working with 5XFAD mice.
format article
author Caroline Bouter
Caroline Irwin
Timon N. Franke
Nicola Beindorff
Yvonne Bouter
author_facet Caroline Bouter
Caroline Irwin
Timon N. Franke
Nicola Beindorff
Yvonne Bouter
author_sort Caroline Bouter
title Quantitative Brain Positron Emission Tomography in Female 5XFAD Alzheimer Mice: Pathological Features and Sex-Specific Alterations
title_short Quantitative Brain Positron Emission Tomography in Female 5XFAD Alzheimer Mice: Pathological Features and Sex-Specific Alterations
title_full Quantitative Brain Positron Emission Tomography in Female 5XFAD Alzheimer Mice: Pathological Features and Sex-Specific Alterations
title_fullStr Quantitative Brain Positron Emission Tomography in Female 5XFAD Alzheimer Mice: Pathological Features and Sex-Specific Alterations
title_full_unstemmed Quantitative Brain Positron Emission Tomography in Female 5XFAD Alzheimer Mice: Pathological Features and Sex-Specific Alterations
title_sort quantitative brain positron emission tomography in female 5xfad alzheimer mice: pathological features and sex-specific alterations
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/55813cdb89144d8a9fe5d94d8bb4ad80
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AT timonnfranke quantitativebrainpositronemissiontomographyinfemale5xfadalzheimermicepathologicalfeaturesandsexspecificalterations
AT nicolabeindorff quantitativebrainpositronemissiontomographyinfemale5xfadalzheimermicepathologicalfeaturesandsexspecificalterations
AT yvonnebouter quantitativebrainpositronemissiontomographyinfemale5xfadalzheimermicepathologicalfeaturesandsexspecificalterations
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