Summary of Deleye et al., (2017)

Deleye et al., (2017) used transgenic mice to understand the effects of how Alzeimer disease pathogen is affected by the chronic administration of B-site amyloid precursor protein (APP) – cleaving enzyme (BACE) inhibitor. This study was based on the understanding that Alzeimer disease is characterized by amyloid-B plaques, neurofibrially tangles, inflammation and neuronal loss on top of being capable of attacking the neural system. To observe the activities of the pathogens without the use of invasive techniques, molecular imaging is necessary both to human and animal specimens with the help of PET tracers. To further the pathogenic activities access, inflammations can be accessed through the use of agents that target the mitochondrial membrane translocator membrane and the glucose analogue. The non-invasive technique helps with the use of an animal for more times.

To initiate the proteolytic processing, amyloidogenic pathway was used. The specimen, TG mice was able to display some features of Azheimer disease, for instance, amyloid-B deposition, gliosis, loss of dendritic spines, and cognitive deficits. The study used both Wild-type and TG mice which were treated to with BACE inhibitor. Outcomes measured included brain function, amyloid pathology, and neuroinflammation. To measure these outcomes, small-animal PET imaging was used.

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Materials in the study included animals which were treated according to the European Ethics Committee which was approved by the local animal Experimental Ethical Committee in Antwerp Belgium. The need for effective studying of the animals called for grouping of the animals in small groups of 7 housed in a cage which was environmentally controlled. With the TG mice, deposition of AB began at week 6 of age. Mature tau tangles were not formed at this age. To control the study, age matched litttermates were used in the all-female mice sample population. 

BACE inhibitor, which is a potent brain-penetrating inhibitor was used to treat the mice. Both the TG and the WT littermates were randomly divided into 2 groups (thus 4 groups of 28 mice each in the end). A 40% Captisol solution was given to the mice daily from week 7 of age.

To acquire and process the image, a radio tracker was administered throught the tail vein to awake the mice and before scanning, the animals were anesthetized through inhalation. A head to head configuration of was done to perform the PET imaging. Heated air was used to maintain core body tempertature. PMOD software was used to process the images which were CT. to conduct statistical analysis, JMP Pro was used besides the GraphPad Prism by employing a linear mixed model to investigate the relationship.

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