Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch Gene

The mechanisms that initiate dementia are poorly understood and there are currently no treatments that can slow their progression. The identification of key genes and molecular pathways that may trigger dementia should help reveal potential therapeutic reagents. In this study, SWItch Miner software was used to identify phosphodiesterase 4D-interacting protein as a key factor that may lead to the development of Alzheimer's disease, vascular dementia, and frontotemporal dementia. Inflammation, PI3K-AKT, and ubiquitin-mediated proteolysis were identified as the main pathways that are dysregulated in these dementias. All of these dementias are regulated by 12 shared transcription factors. Protein-chemical interaction network analysis of dementia switch genes revealed that valproic acid may be neuroprotective for these dementias. Collectively, we identified shared and unique dysregulated gene expression, pathways and regulatory factors among dementias. New key mechanisms that lead to the development of dementia were revealed and it is expected that these data will advance personalized medicine for patients.