Neuronally enriched microvesicle RNAs are differentially expressed in the serums of Parkinson’s patients
BackgroundCirculating small RNAs (smRNAs) originate from diverse tissues and organs. Previous studies investigating smRNAs as potential biomarkers for Parkinson’s disease (PD) have yielded inconsistent results. We investigated whether smRNA profiles from neuronally-enriched serum exosomes and microv...
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| Format: | Article |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1145923/full |
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| author | Morris A. Aguilar Morris A. Aguilar Shauna Ebanks Havell Markus Mechelle M. Lewis Mechelle M. Lewis Vishal Midya Kent Vrana Xuemei Huang Xuemei Huang Molly A. Hall Molly A. Hall Yuka Imamura Kawasawa Yuka Imamura Kawasawa Yuka Imamura Kawasawa |
| author_facet | Morris A. Aguilar Morris A. Aguilar Shauna Ebanks Havell Markus Mechelle M. Lewis Mechelle M. Lewis Vishal Midya Kent Vrana Xuemei Huang Xuemei Huang Molly A. Hall Molly A. Hall Yuka Imamura Kawasawa Yuka Imamura Kawasawa Yuka Imamura Kawasawa |
| author_sort | Morris A. Aguilar |
| collection | DOAJ |
| description | BackgroundCirculating small RNAs (smRNAs) originate from diverse tissues and organs. Previous studies investigating smRNAs as potential biomarkers for Parkinson’s disease (PD) have yielded inconsistent results. We investigated whether smRNA profiles from neuronally-enriched serum exosomes and microvesicles are altered in PD patients and discriminate PD subjects from controls.MethodsDemographic, clinical, and serum samples were obtained from 60 PD subjects and 40 age- and sex-matched controls. Exosomes and microvesicles were extracted and isolated using a validated neuronal membrane marker (CD171). Sequencing and bioinformatics analyses were used to identify differentially expressed smRNAs in PD and control samples. SmRNAs also were tested for association with clinical metrics. Logistic regression and random forest classification models evaluated the discriminative value of the smRNAs.ResultsIn serum CD171 enriched exosomes and microvesicles, a panel of 29 smRNAs was expressed differentially between PD and controls (false discovery rate (FDR) < 0.05). Among the smRNAs, 23 were upregulated and 6 were downregulated in PD patients. Pathway analysis revealed links to cellular proliferation regulation and signaling. Least absolute shrinkage and selection operator adjusted for the multicollinearity of these smRNAs and association tests to clinical parameters via linear regression did not yield significant results. Univariate logistic regression models showed that four smRNAs achieved an AUC ≥ 0.74 to discriminate PD subjects from controls. The random forest model had an AUC of 0.942 for the 29 smRNA panel.ConclusionCD171-enriched exosomes and microvesicles contain the differential expression of smRNAs between PD and controls. Future studies are warranted to follow up on the findings and understand the scientific and clinical relevance. |
| first_indexed | 2024-03-13T01:01:50Z |
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| id | doaj.art-313c638db17f417b971da0f5798c8ee5 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-03-13T01:01:50Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-313c638db17f417b971da0f5798c8ee52023-07-06T11:22:44ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-07-011710.3389/fnins.2023.11459231145923Neuronally enriched microvesicle RNAs are differentially expressed in the serums of Parkinson’s patientsMorris A. Aguilar0Morris A. Aguilar1Shauna Ebanks2Havell Markus3Mechelle M. Lewis4Mechelle M. Lewis5Vishal Midya6Kent Vrana7Xuemei Huang8Xuemei Huang9Molly A. Hall10Molly A. Hall11Yuka Imamura Kawasawa12Yuka Imamura Kawasawa13Yuka Imamura Kawasawa14Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United StatesHuck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, United StatesDepartment of Neurology, College of Medicine, The Pennsylvania State University, Hershey, PA, United StatesDepartment of Neurology, College of Medicine, The Pennsylvania State University, Hershey, PA, United StatesDepartment of Neurology, College of Medicine, The Pennsylvania State University, Hershey, PA, United StatesDepartment of Pharmacology, College of Medicine, The Pennsylvania State University, Hershey, PA, United StatesDepartment of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Pharmacology, College of Medicine, The Pennsylvania State University, Hershey, PA, United StatesDepartment of Neurology, College of Medicine, The Pennsylvania State University, Hershey, PA, United StatesDepartment of Pharmacology, College of Medicine, The Pennsylvania State University, Hershey, PA, United StatesDepartment of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United StatesHuck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, United StatesDepartment of Pharmacology, College of Medicine, The Pennsylvania State University, Hershey, PA, United StatesDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, United StatesInstitute for Personalized Medicine, College of Medicine, The Pennsylvania State University, Hershey, PA, United StatesBackgroundCirculating small RNAs (smRNAs) originate from diverse tissues and organs. Previous studies investigating smRNAs as potential biomarkers for Parkinson’s disease (PD) have yielded inconsistent results. We investigated whether smRNA profiles from neuronally-enriched serum exosomes and microvesicles are altered in PD patients and discriminate PD subjects from controls.MethodsDemographic, clinical, and serum samples were obtained from 60 PD subjects and 40 age- and sex-matched controls. Exosomes and microvesicles were extracted and isolated using a validated neuronal membrane marker (CD171). Sequencing and bioinformatics analyses were used to identify differentially expressed smRNAs in PD and control samples. SmRNAs also were tested for association with clinical metrics. Logistic regression and random forest classification models evaluated the discriminative value of the smRNAs.ResultsIn serum CD171 enriched exosomes and microvesicles, a panel of 29 smRNAs was expressed differentially between PD and controls (false discovery rate (FDR) < 0.05). Among the smRNAs, 23 were upregulated and 6 were downregulated in PD patients. Pathway analysis revealed links to cellular proliferation regulation and signaling. Least absolute shrinkage and selection operator adjusted for the multicollinearity of these smRNAs and association tests to clinical parameters via linear regression did not yield significant results. Univariate logistic regression models showed that four smRNAs achieved an AUC ≥ 0.74 to discriminate PD subjects from controls. The random forest model had an AUC of 0.942 for the 29 smRNA panel.ConclusionCD171-enriched exosomes and microvesicles contain the differential expression of smRNAs between PD and controls. Future studies are warranted to follow up on the findings and understand the scientific and clinical relevance.https://www.frontiersin.org/articles/10.3389/fnins.2023.1145923/fullParkinson’s diseaseexosomemicrovesiclesmall RNAbiomarkersregression |
| spellingShingle | Morris A. Aguilar Morris A. Aguilar Shauna Ebanks Havell Markus Mechelle M. Lewis Mechelle M. Lewis Vishal Midya Kent Vrana Xuemei Huang Xuemei Huang Molly A. Hall Molly A. Hall Yuka Imamura Kawasawa Yuka Imamura Kawasawa Yuka Imamura Kawasawa Neuronally enriched microvesicle RNAs are differentially expressed in the serums of Parkinson’s patients Frontiers in Neuroscience Parkinson’s disease exosome microvesicle small RNA biomarkers regression |
| title | Neuronally enriched microvesicle RNAs are differentially expressed in the serums of Parkinson’s patients |
| title_full | Neuronally enriched microvesicle RNAs are differentially expressed in the serums of Parkinson’s patients |
| title_fullStr | Neuronally enriched microvesicle RNAs are differentially expressed in the serums of Parkinson’s patients |
| title_full_unstemmed | Neuronally enriched microvesicle RNAs are differentially expressed in the serums of Parkinson’s patients |
| title_short | Neuronally enriched microvesicle RNAs are differentially expressed in the serums of Parkinson’s patients |
| title_sort | neuronally enriched microvesicle rnas are differentially expressed in the serums of parkinson s patients |
| topic | Parkinson’s disease exosome microvesicle small RNA biomarkers regression |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1145923/full |
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