The role of yRNA and yRNA fragmentation in development and progression of Alzheimer's disease
Despite intense research efforts, there is still no available treatment or cure for Alzheimer's Disease (AD). The aim of this project is to investigate molecular and pathophysiological mechanisms underlying AD by analysing yRNA in exosomes and identify a signature that is unique for AD. Further, we aim to define whether the enzyme Endonuclease V (EndoV) is involved in sorting yRNA into exosomes, and whether this affects AD related pathology in the brain. In this study we will investigate dysregulation of yRNA in AD, and whether EndoV is involved in AD pathology in a transgenic mice model of AD, and in mice with AD lacking EndoV. We will collect whole blood at different time points (1, 2.5, 4.5 and 9 months of age) to analyse exosomes in plasma. During these time points mice will be evaluated using the Y-maze, elevated zero maze and open field test to assess cognitive behaviour. At the end of the experiment, brains will be collected for histopathological analysis.
The proposed project aims to add new bricks to the puzzle of pathophysiological mechanisms underlying AD, and has the potential to discover a novel signature for AD that in the future can be developed to a diagnostic test for AD. Moreover, better understanding of what goes wrong when AD develops is a prerequisite for developing new treatment options for this devastating disease where presently no cure exists.
Experiments will be carefully planned to avoid using more animals than necessary. For colony maintenance and generation of adequate number of experimental animals of four different strains (WT, 5XFAD, EndoV KO and 5XFAD/EndoV KO), we estimate the total number of animals applied for here is 1426.
To date there is no in vitro model of neurodegenerative diseases that can recapitulate the complexity of the human brain, therefore we still rely on animal models for research on neurodegenerative diseases. However, to reduce the number of animals in this project as much as possible we will also use an in vitro human brain organoid model and blood plasma samples from clinical AD patients to test findings from the animal studies.
The proposed project aims to add new bricks to the puzzle of pathophysiological mechanisms underlying AD, and has the potential to discover a novel signature for AD that in the future can be developed to a diagnostic test for AD. Moreover, better understanding of what goes wrong when AD develops is a prerequisite for developing new treatment options for this devastating disease where presently no cure exists.
Experiments will be carefully planned to avoid using more animals than necessary. For colony maintenance and generation of adequate number of experimental animals of four different strains (WT, 5XFAD, EndoV KO and 5XFAD/EndoV KO), we estimate the total number of animals applied for here is 1426.
To date there is no in vitro model of neurodegenerative diseases that can recapitulate the complexity of the human brain, therefore we still rely on animal models for research on neurodegenerative diseases. However, to reduce the number of animals in this project as much as possible we will also use an in vitro human brain organoid model and blood plasma samples from clinical AD patients to test findings from the animal studies.