Accepted_test

Despite the research community contributing significant efforts in studying pathogenesis of Alzheimer disease, understanding the molecular and structural changes in the cells remains incomplete. Alternative splicing (AS) and post translational modifications represent the powerful mechanisms of regulating protein function. However, the diversity of alternatively spliced proteins and co-occurrence of different types of post translational modifications and their role in pathogenesis of Alzheimer disease are not investigated. Detection of AS at protein level and multiple protein modifications is a challenging task. In this study we developed mass spectrometry based bioinformatic approaches for discovery of the alternative splicing and amino acid substitutions translated into proteins in Alzheimer's disease as well as novel post translational modifications including modifications of the alternatively spliced proteins and characterization of their functional implications. Using the post mortem brain tissues from 300 AD patients and 200 healthy individuals, we demonstrate that the developed bioinformatic pipelines represent powerful tools to follow genomic events translated to proteins and pretended for reproducibility and novelty.