Transcription‐based drug repurposing in Alzheimer disease psychosis

Background There are at least 50 million people with Alzheimer’s Disease (AD) or other dementias worldwide. About 50% of AD may develop psychotic symptoms (delusions and hallucinations). However, there is no effective pharmacological therapy for psychosis in all current treatments based on antipsychotics originally designed disorders like schizophrenia. In this study, we identify the molecular signature post-mortem brain samples then use connectivity map (CMAP) library network-based cellular signatures (LINC) to predict candidate drugs disease transcriptional signature. Method We generated RNA-Seq data (Illumina Stranded mRNA Prep) compared gene expression levels across 4 groups: Control, (AD), Delusions (ADD), both Hallucinations (ADDH). The final identified differentially expressed up down-regulated genes (DEGs) were used as query CMAP LINC databases that could potentially reverse samples. To investigate mechanisms effect repurposed it, a drug-target interaction network was reconstructed combined human interactome. Enrichment analysis identifies psychosis-related pathways potential nominated have them. Result After filtering out common DEGs, 357, 171, 66 unique remained AD, ADD, ADDH sets, respectively. signatureSearch package search transcriptome against LINC. top ranked drugs, negative scores, selected results. Gene set enrichment drug target presented some key activities related psychiatric disorders. For example, serotonin receptor signalling pathway one most over-represented ADD groups. Conclusion This study can improve our understanding underlying psychosis. be clinical trials provide valuable knowledge future research.