Common microRNA regulated pathways in Alzheimer’s and Parkinson’s disease
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ABSTRACT:
SUBMITTER: Awuson-David B
PROVIDER: S-EPMC10502311 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectiveThe goal of this study was to compare the microRNA (miRNA) profile of Parkinson's disease (PD) frontal cortex with normal control brain, allowing for the identification of PD specific signatures as well as study the disease-related phenotypes of onset age and dementia.MethodsSmall RNA sequence analysis was performed from prefrontal cortex for 29 PD samples and 33 control samples. After sample QC, normalization and batch correction, linear regression was employed to identify miRNAs altered in PD, and a PD classifier was developed using weighted voting class prediction. The relationship of miRNA levels to onset age and PD with dementia (PDD) was also characterized in case-only analyses.ResultsOne twenty five miRNAs were differentially expressed in PD at a genome-wide level of significance (FDR q < 0.05). A set of 29 miRNAs classified PD from non-diseased brain (93.9% specificity, 96.6% sensitivity). The majority of differentially expressed miRNAs (105/125) showed an ordinal relationship from control, to PD without dementia (PDN), to PDD. Among PD brains, 36 miRNAs classified PDD from PDN (sensitivity = 81.2%, specificity = 88.9%). Among differentially expressed miRNAs, miR-10b-5p had a positive association with onset age (q = 4.7e-2).ConclusionsBased on cortical miRNA levels, PD brains were accurately classified from non-diseased brains. Additionally, the PDD miRNA profile exhibited a more severe pattern of alteration among those differentially expressed in PD. To evaluate the clinical utility of miRNAs as potential clinical biomarkers, further characterization and testing of brain-related miRNA alterations in peripheral biofluids is warranted.
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Project description:Alzheimer's disease (AD) and Parkinson's disease (PD) cause significant neuronal loss and severely impair daily living. Despite different clinical manifestations, these disorders share common pathological molecular hallmarks, including mitochondrial dysfunction and synaptic degeneration. A detailed comparison of molecular changes at single-cell resolution in the cortex, as one of the main brain regions affected in both disorders, may reveal common susceptibility factors and disease mechanisms. We performed single-cell transcriptomic analyses of post-mortem cortical tissue from AD and PD subjects and controls to identify common and distinct disease-associated changes in individual genes, cellular pathways, molecular networks, and cell-cell communication events, and to investigate common mechanisms. The results revealed significant disease-specific, shared, and opposing gene expression changes, including cell type-specific signatures for both diseases. Hypoxia signaling and lipid metabolism emerged as significantly modulated cellular processes in both AD and PD, with contrasting expression alterations between the two diseases. Furthermore, both pathway and cell-cell communication analyses highlighted shared significant alterations involving the JAK-STAT signaling pathway, which has been implicated in the inflammatory response in several neurodegenerative disorders. Overall, the analyses revealed common and distinct alterations in gene signatures, pathway activities, and gene regulatory subnetworks in AD and PD. The results provide insights into coordinated changes in pathway activity and cell-cell communication that may guide future diagnostics and therapeutics.
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