Investigating the epigenetic role of Rbbp7 in Alzheimer's Disease
Alzheimer's disease (AD) affects over 6.9 million people over the age of 65 in the US. The pathophysiology hallmarks of AD include amyloid plaques and tau neurofibrillary tangles, however, the exact etiology remains elusive leading to a lack of effective treatment options. Our previous analysis highlights the downregulation of Rbbp7 in post-mortem brains of AD-affected patients compared with matched healthy controls. This downregulation directly correlated with tau acetylation and consequently tau phosphorylation. Moreover, Rbbp7 protein levels were significantly decreased in AD-mice models compared to mocks, but no decreases were found in APP/PS1 mice that lack tau pathology. Finally, Rbbp7 expression negatively correlates with neuropathological hallmarks of AD. Our aim is to understand how Rbbp7 exerts its protective role and identify the targets Rbbp7 directly modulates. To achieve this, we overexpressed Rbbp7 in mouse models and thanks to Next Generation Sequencing we will be able to analyze the specific gene expression changes and identify epigenetic regulated locus through the ATAC-seq assay. We were able to optimize ATAC-seq protocol to improve the quality of our libraries and will perform a protein interaction analysis with co-immunoprecipitation and liquid chromatography coupled with mass spectrometry to identify downstream targets of Rbbp7. Finally, we will be able to assess and elucidate the protective role of Rbbp7 through a multi-omics approach and reveal new possible therapeutic targets.
