In-vivo-Diagnostik und Therapiemonitoring mittels 18F-FDG-Positronenemissionstomographie im Tg4-42 Alzheimer-Mausmodell

by Caroline Irwin
Doctoral thesis
Date of Examination:2025-04-14
Date of issue:2025-04-14
Advisor:PD Dr. Yvonne Bouter
Referee:PD Dr. Yvonne Bouter
Referee:Dr. Johannes Professor Uhlig
Persistent Address: http://dx.doi.org/10.53846/goediss-11202

 

 

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Abstract

English

In this study, two groups of Alzheimer's model mice of the Tg4-42 type were injected intravenously with 18F-FDG at the age of 7 months and 3 months. Subsequently, the 18F-FDG uptake of the brain was visualized by PET/MRI. Similarly, wild-type animals of the C57Bl/6J type were examined as a control group for their 18F-FDG uptake at 7 months of age. 18F-FDG-PET is able to visualize the reduced glucose metabolism in vivo, which essentially depends on the number of neurons and the synaptic activity of the brain. In comparison, it could be shown that the older Tg4-42 mice exhibit a lower 18F-FDG uptake in the entire brain as well as in almost all brain regions and thus a reduced glucose metabolism compared to wild-type animals. The young Tg4-42 mice showed no significant change over the entire brain. In the brain regions of the hypothalamus, the amygdala and the midbrain there was already a reduced glucose metabolism compared to the wild-type mice. Significant changes were also visible in the comparison of young to older Tg4-42 mice. The older Tg4-42 mice showed a significantly reduced 18F-FDG uptake in the whole brain and over all brain regions except the amygdala, in contrast to the young Tg4-42 mice. This demonstrated that 18F-FDG PET is able to visualize reduced age-dependent glucose metabolism in vivo, consistent with the results of Alzheimer's patients in the Tg4-42 mouse model. In the second step, one group of Tg4-42 mice was treated preventively at the age of 3 months (before the onset of neuronal loss) with tetrahydrocannabinol and another group at the age of 3 months with cannabidiol for 42 days each. At the age of 7 months these groups were examined by 18F-FDG-PET/MRI. Compared to untreated Tg4-42 mice of the same age, mice treated with tetrahydrocannabinol showed a significant increase in glucose uptake in the brain areas of the hippocampus, hypothalamus and forebrain. The group treated with cannabidiol showed no significant change in glucose metabolism compared to the untreated control group.
Keywords: Alzheimer's; FDG-PET; Tg4-42; THC; CBD