Orchestration of a blood-derived and ADARB1-centred network in Alzheimer's and Parkinson's disease

The peripheral immune system is thought to influence the pathogenesis of the central nervous system in Alzheimer’s disease (AD) and Parkinson’s disease (PD). This study aimed to investi-gate the characteristics of peripheral leukocytes in AD and PD by comprehensively analyzing the transcriptomic and metabolic features in the blood (NCONTROL = 15; NAD = 11; NPD = 13). The study found an ADARB1-centered module that was associated with diagnosis, phenethylamine, and glutamate. The module consisted of ADARB1, a vital RNA-editing enzyme, LINC02960, and 109 miRNAs. The study also predicted that the ADARB1 and involved regulators were targeted by miRNAs in the ADARB1 module. The integrated analysis of transcriptome and metabolic panel revealed a central role of ADARB1, miR-199b-5p, miR-26a, miR-450b-5p, miR-34c-5p, glutamate and phenethylamine in the regulatory relationships. The study highlights a set of synergetic non-coding RNA related to ADARB1 in the blood ecosystem of AD and PD with dy-namic glutamate and phenethylamine, providing new insights into the pathogenesis of these diseases. To better understand the relationship between peripheral blood leukocyte and brain-based epigenetic activity in the context of Alzheimer's disease (AD) and Parkinson's disease (PD), we conducted a pilot study on peripheral blood leukocytes by comprehensively analysing transcriptomic and metabolic features in blood (NCONTROL = 15; NAD = 11; NPD = 13). Using next-generation sequencing, we identified 766 miRNAs and 19,512 mRNAs/lncRNAs after removing low-quality reads and low-abundance RNAs. Using LC-MS/MS, we identified 8 DE metabolites of 7 short-chain fatty acids and 23 neurotransmitters. Using a comprehensive integrative analysis of multi-omics data, we identified an ADARB1-centred co-expression sub-network consisting of ADARB1, LINC02960 and 109 miRNAs simultaneously correlated with diagnosis, glutamate and phenethylamine. A putative interaction within the ADARB1 module was raised in the blood ecosystem of AD and PD. **RAW data not provided due to relevant law**