A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls

The most frequently used biomarkers to support the diagnosis of Alzheimer’s Disease (AD) are Aβ42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyl...

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Vydáno v:	International journal of molecular sciences Ročník 23; číslo 21; s. 13232
Hlavní autoři:	Piscopo, Paola, Manzini, Valeria, Rivabene, Roberto, Crestini, Alessio, Le Pera, Loredana, Pizzi, Elisabetta, Veroni, Caterina, Talarico, Giuseppina, Peconi, Martina, Castellano, Anna Elisa, D’Alessio, Carmelo, Bruno, Giuseppe, Corbo, Massimo, Vanacore, Nicola, Lacorte, Eleonora
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Switzerland MDPI AG 31.10.2022 MDPI
Témata:	Accuracy Age Alzheimer Disease - diagnosis Alzheimer Disease - genetics Alzheimer's disease Biomarkers Cluster analysis Cognitive Dysfunction - diagnosis Cognitive Dysfunction - genetics Gene loci Humans MicroRNAs MicroRNAs - genetics Pilot Projects Plasma Population RNA - genetics RNA polymerase RNA, Circular - blood RNA, Circular - genetics RNA, Untranslated Statistical significance Validation studies MCI AD circRNA biomarkers circular RNA microarray Real-Time PCR mild cognitive impairment Alzheimer Disease
ISSN:	1422-0067, 1661-6596, 1422-0067
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Abstract	The most frequently used biomarkers to support the diagnosis of Alzheimer’s Disease (AD) are Aβ42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyloid deposition. These tests are rather complex and invasive and not easily applicable to clinical practice. Circulating non-coding RNAs, which are inherently stable and easy to manage, have been reported as promising biomarkers for central nervous system conditions. Recently, circular RNAs (circRNAs) as a novel class of ncRNAs have gained attention. We carried out a pilot study on five participants with AD and five healthy controls (HC) investigating circRNAs by Arraystar Human Circular RNA Microarray V2.0. Among them, 26 circRNAs were differentially expressed (FC ≥ 1.5, p < 0.05) in participants with AD compared to HC. From a top 10 of differentially expressed circRNAs, a validation study was carried out on four up-regulated (hsa_circRNA_050263, hsa_circRNA_403959, hsa_circRNA_003022, hsa_circRNA_100837) and two down-regulated (hsa_circRNA_102049, hsa_circRNA_102619) circRNAs in a larger population. Moreover, five subjects with mild cognitive impairment (MCI) were investigated. The analysis confirmed the upregulation of hsa_circRNA_050263, hsa_circRNA_403959, and hsa_circRNA_003022 both in subjects with AD and in MCI compared to HCs. We also investigated all microRNAs potentially interacting with the studied circRNAs. The GO enrichment analysis shows they are involved in the development of the nervous system, and in the cellular response to nerve growth factor stimuli, protein phosphorylation, apoptotic processes, and inflammation pathways, all of which are processes related to the pathology of AD.
AbstractList	The most frequently used biomarkers to support the diagnosis of Alzheimer’s Disease (AD) are Aβ42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyloid deposition. These tests are rather complex and invasive and not easily applicable to clinical practice. Circulating non-coding RNAs, which are inherently stable and easy to manage, have been reported as promising biomarkers for central nervous system conditions. Recently, circular RNAs (circRNAs) as a novel class of ncRNAs have gained attention. We carried out a pilot study on five participants with AD and five healthy controls (HC) investigating circRNAs by Arraystar Human Circular RNA Microarray V2.0. Among them, 26 circRNAs were differentially expressed (FC ≥ 1.5, p < 0.05) in participants with AD compared to HC. From a top 10 of differentially expressed circRNAs, a validation study was carried out on four up-regulated (hsa_circRNA_050263, hsa_circRNA_403959, hsa_circRNA_003022, hsa_circRNA_100837) and two down-regulated (hsa_circRNA_102049, hsa_circRNA_102619) circRNAs in a larger population. Moreover, five subjects with mild cognitive impairment (MCI) were investigated. The analysis confirmed the upregulation of hsa_circRNA_050263, hsa_circRNA_403959, and hsa_circRNA_003022 both in subjects with AD and in MCI compared to HCs. We also investigated all microRNAs potentially interacting with the studied circRNAs. The GO enrichment analysis shows they are involved in the development of the nervous system, and in the cellular response to nerve growth factor stimuli, protein phosphorylation, apoptotic processes, and inflammation pathways, all of which are processes related to the pathology of AD. The most frequently used biomarkers to support the diagnosis of Alzheimer’s Disease (AD) are Aβ42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyloid deposition. These tests are rather complex and invasive and not easily applicable to clinical practice. Circulating non-coding RNAs, which are inherently stable and easy to manage, have been reported as promising biomarkers for central nervous system conditions. Recently, circular RNAs (circRNAs) as a novel class of ncRNAs have gained attention. We carried out a pilot study on five participants with AD and five healthy controls (HC) investigating circRNAs by Arraystar Human Circular RNA Microarray V2.0. Among them, 26 circRNAs were differentially expressed (FC ≥ 1.5, p < 0.05) in participants with AD compared to HC. From a top 10 of differentially expressed circRNAs, a validation study was carried out on four up-regulated (hsa_circRNA_050263, hsa_circRNA_403959, hsa_circRNA_003022, hsa_circRNA_100837) and two down-regulated (hsa_circRNA_102049, hsa_circRNA_102619) circRNAs in a larger population. Moreover, five subjects with mild cognitive impairment (MCI) were investigated. The analysis confirmed the upregulation of hsa_circRNA_050263, hsa_circRNA_403959, and hsa_circRNA_003022 both in subjects with AD and in MCI compared to HCs. We also investigated all microRNAs potentially interacting with the studied circRNAs. The GO enrichment analysis shows they are involved in the development of the nervous system, and in the cellular response to nerve growth factor stimuli, protein phosphorylation, apoptotic processes, and inflammation pathways, all of which are processes related to the pathology of AD.The most frequently used biomarkers to support the diagnosis of Alzheimer’s Disease (AD) are Aβ42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyloid deposition. These tests are rather complex and invasive and not easily applicable to clinical practice. Circulating non-coding RNAs, which are inherently stable and easy to manage, have been reported as promising biomarkers for central nervous system conditions. Recently, circular RNAs (circRNAs) as a novel class of ncRNAs have gained attention. We carried out a pilot study on five participants with AD and five healthy controls (HC) investigating circRNAs by Arraystar Human Circular RNA Microarray V2.0. Among them, 26 circRNAs were differentially expressed (FC ≥ 1.5, p < 0.05) in participants with AD compared to HC. From a top 10 of differentially expressed circRNAs, a validation study was carried out on four up-regulated (hsa_circRNA_050263, hsa_circRNA_403959, hsa_circRNA_003022, hsa_circRNA_100837) and two down-regulated (hsa_circRNA_102049, hsa_circRNA_102619) circRNAs in a larger population. Moreover, five subjects with mild cognitive impairment (MCI) were investigated. The analysis confirmed the upregulation of hsa_circRNA_050263, hsa_circRNA_403959, and hsa_circRNA_003022 both in subjects with AD and in MCI compared to HCs. We also investigated all microRNAs potentially interacting with the studied circRNAs. The GO enrichment analysis shows they are involved in the development of the nervous system, and in the cellular response to nerve growth factor stimuli, protein phosphorylation, apoptotic processes, and inflammation pathways, all of which are processes related to the pathology of AD.
Author	Castellano, Anna Elisa Piscopo, Paola Veroni, Caterina Corbo, Massimo Peconi, Martina Lacorte, Eleonora Manzini, Valeria Pizzi, Elisabetta Talarico, Giuseppina Le Pera, Loredana Rivabene, Roberto Crestini, Alessio Bruno, Giuseppe D’Alessio, Carmelo Vanacore, Nicola
AuthorAffiliation	6 Department of Neurorehabilitation Sciences, Casa Cura Policlinico, 20144 Milan, MI, Italy 4 Department of Human Neuroscience, University of Rome “Sapienza”, 00185 Rome, RM, Italy 1 Department of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, RM, Italy 3 Servizio Grandi Strumentazioni e Core Facilities, Istituto Superiore di Sanità, 00161 Rome, RM, Italy 5 Department of Neurology, IRCCS Neuromed Institute, 86077 Pozzilli, IS, Italy 2 EBRI Rita Levi-Montalcini Foundation, 00161 Rome, RM, Italy 7 National Center for Disease Prevention ad Heath Promotion, Istituto Superiore di Sanità, 00162 Rome, RM, Italy
AuthorAffiliation_xml	– name: 5 Department of Neurology, IRCCS Neuromed Institute, 86077 Pozzilli, IS, Italy – name: 3 Servizio Grandi Strumentazioni e Core Facilities, Istituto Superiore di Sanità, 00161 Rome, RM, Italy – name: 1 Department of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, RM, Italy – name: 7 National Center for Disease Prevention ad Heath Promotion, Istituto Superiore di Sanità, 00162 Rome, RM, Italy – name: 2 EBRI Rita Levi-Montalcini Foundation, 00161 Rome, RM, Italy – name: 6 Department of Neurorehabilitation Sciences, Casa Cura Policlinico, 20144 Milan, MI, Italy – name: 4 Department of Human Neuroscience, University of Rome “Sapienza”, 00185 Rome, RM, Italy
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Copyright	2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2022 by the authors. 2022
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Snippet	The most frequently used biomarkers to support the diagnosis of Alzheimer’s Disease (AD) are Aβ42, total-Tau, and phospho-tau protein levels in CSF. Moreover,...
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SubjectTerms	Accuracy Age Alzheimer Disease - diagnosis Alzheimer Disease - genetics Alzheimer's disease Biomarkers Cluster analysis Cognitive Dysfunction - diagnosis Cognitive Dysfunction - genetics Gene loci Humans MicroRNAs MicroRNAs - genetics Pilot Projects Plasma Population RNA - genetics RNA polymerase RNA, Circular - blood RNA, Circular - genetics RNA, Untranslated Statistical significance Validation studies
Title	A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls
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