NeuralCipher Research overview
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IntroductionBlood-based biomarkers that can aid diagnosis of Parkinson's Disease (PD) dementia (PDD), and predict PDD onset in people with PD are urgently needed. Plasma small extracellular vesicles (SEV) reflect molecular changes in living human brain. Next-generation RNA-sequencing (RNA-Seq) of PDD plasma SEV can advance our understanding of PDD molecular pathology, and identify blood-based biomarkers. Hence, we conducted the first comprehensive transcriptomic analysis of PDD plasma SEV.MethodsWe investigated plasma SEV RNA of PDD, PD, and people without PD or dementia (Controls) using RNA-Seq (n = 15/group; N = 45). SEV were separated by ultracentrifugation, and characterized by cryo-transmission electron microscopy. We identified differentially expressed genes (DEGs) in PDD plasma SEV using an edgeR-based data analysis pipeline and verified them by high-throughput qPCR. We assessed functional implications of identified DEGs using Ingenuity Pathway and causal network analyses.ResultsWe identified 51 transcriptome-wide significant (edgeR q ConclusionFuture research on the identified dysfunctional molecular pathways may facilitate discovery of novel therapeutic targets for PDD. Diagnostic biomarker potential of the derived multiplex RNA biomarker assays should be investigated by larger clinical studies.
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