The pathophysiological cascade leading to Alzheimer’s disease is characterized by the accumulation of destructive β-amyloid in the brain. Convincing evidence has also shown that cerebral energy hypometabolism and an overproduction of translocator protein during neuroinflammation, as well as deficits in the endocannabinoid system, play major roles in progression of the disease. Monitoring temporal changes inside the diseased brain with noninvasive positron emission tomography (PET) would be a unique translational tool, bridging the gap between disease models and patients and aiding in the discovery of disease-modifying therapies against Alzheimer’s disease. 

The aim of this thesis was to evaluate the translational feasibility of cerebral glucose metabolism targeting PET tracer 18F-FDG in APPswe-PSIdE9, Tg2576, and APP/PS1-21 mouse models of Alzheimer’s disease. In addition, this thesis aimed to examine the suitability of neuroinflammation-specific protein targeting tracer 18F-DPA-714 for longitudinal follow-up in aging APP/PS1-21 mice and whether it correlates with changes in glucose metabolism. Furthermore, the translational applicability of 18F-FMPEP-d2 was evaluated as a tool to assist in preclinical research targeting cannabinoid receptor 1 (CB1R) in wild-type and APP/PS1-21 mice. 

Of the tested models, APP/PS1-21 mice demonstrated the most aggressive β-amyloid pathology. Furthermore, repeated PET scans with 18F-FDG and 18F-DPA-714 detected progressive glucose hypometabolism and neuroinflammation in the APP/PS1-21 model as the mice aged. However in the APPswe-PSIdE9 and Tg2576 mouse models, only a weak or non-altered glucose metabolism was observed. 18F-FMPEP-d2 was able to reveal altered CB1R availability when aging APP/PS1- 21 mice were followed with repeated PET scans. 

This thesis work demonstrated that Alzheimer’s disease mouse models differ in terms of amyloidosis and cerebral glucose metabolism, which creates challenges when comparing the research results between the models. The feasibility of 18F-FDG small animal PET depends on the chosen disease model and environmental factors. In the APP/PS1-21 model, longitudinal 18FFMPEP- d2 and 18F-DPA-714 PET scans were able to demonstrate pathological features related to Alzheimer´s disease, which were confirmed by ex vivo examinations.