Positronen-Emissions-Tomographie im 5XFAD-Mausmodell der Alzheimer Erkrankung: eine valide Methode für In-vivo Diagnostik und Therapiemonitoring

by Timon Niklas Franke
Doctoral thesis
Date of Examination:2024-06-26
Date of issue:2024-06-24
Advisor:PD Dr. Yvonne Bouter
Referee:PD Dr. Yvonne Bouter
Referee:Prof. Dr. Jan-Alexander Bucerius
Referee:Prof. Dr. Margarete Schön
Persistent Address: http://dx.doi.org/10.53846/goediss-10563

 

 

Files in this item

Name:Franke_Timon_Dissertation_final.pdf
Size:1.58Mb
Format:PDF

This file will be freely accessible after 2025-06-24.

Abstract

English

PET is increasingly becoming an important method of Alzheimer's research. Since previous studies on PET in preclinical mouse models of Alzheimer's disease were inconsistent and in some cases contradictory, it was the primary aim of this work to investigate whether the modern instruments of clinical Alzheimer's diagnostics, 18F-FDG-PET and 18F-FBB-PET, can be applied to a preclinical mouse model. The 5XFAD model was selected as a suitable mouse model for this purpose. It is characterized by massive Aβ plaque pathology and significant neuronal loss. FDG-PET is used to visualize glucose uptake in the brain. As glucose turnover in the brain is largely dependent on synaptic activity, reduced FDG uptake is used as a diagnostic criteria for the neuronal loss in Alzheimer's disease. In this study it was shown that 5XFAD mice at the age of 7 months showed significantly reduced FDG uptake in the brain as a whole and in individual brain regions. Amyloid PET is used to detect Aβ deposits. The 18F-FBB tracer is an established established marker in clinical practice for the diagnosis of human Alzheimer's disease. In this study, the 5XFAD mice - corresponding to human Alzheimer's patients - showed a significantly increased FBB uptake in specific Alzheimer's relevant brain regions. Overall, the applicability of FDG- and FBB-PET diagnostics on the 5XFAD mouse model was successfully demonstrated. In the second part of the study, the effect of a 6-week CBD therapy on 5-month-old 5XFAD females was investigated using PET. This showed a significant reduction in FDG uptake in the brains of the treated animals compared to untreated 5XFAD animals. The amyloid PET, however, showed a significant reduction in the FBB uptake of the treated animals in individual brain regions, particularly in the hippocampus. To compare these results, the histopathological Aβ-staining with thioflavin and the established behavioral tests Novel-Object-Recognition and Morris Water Maze were used. Here the performance of the 5XFAD animals in both tests was improved by the CBD treatment compared to untreated 5XFAD females. This raises questions regarding the reduced FDG uptake in the treated animals in the PET. The reduction in Aβ deposits found in the thioflavin staining is consistent with the significant reduction in FBB uptake in the hippocampus. Overall PET with 18F-FDG and 18F-FBB seems to be a valuable tool for preclinical therapy monitoring in the 5XFAD mouse model.
Keywords: Alzheimer's; 5XFAD; PET; FDG; Florbetaben; Cannabidiol