한빛사 논문
Sojung Yoon1,30, Sung Eun Kim1,30, Younhee Ko2, Gwang Hun Jeong3, Keum Hwa Lee4, Jinhee Lee5, Marco Solmi6,7,8,9, Louis Jacob10,11, Lee Smith12, Andrew Stickley13,14, Andre F. Carvalho15,16, Elena Dragioti17, Andreas Kronbichler18, Ai Koyanagi11,19, Sung Hwi Hong1, Trevor Thompson20, Hans Oh21, Gonzalo Salazar de Pablo22,23,24, Joaquim Radua22,25,26, Jae Il Shin4,* and Paolo Fusar-Poli22,27,28,29
1Yonsei University College of Medicine, Seoul, Republic of Korea. 2Division of Biomedical Engineering, Hankuk University of Foreign Studies, Kyoungki-do, Republic of Korea. 3College of Medicine, Gyeongsang National University, Jinju, Republic of Korea. 4Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea. 5Department of Psychiatry, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. 6Department of Psychiatry, University of Ottawa, Ontario, ON, Canada. 7Department of Mental Health, The Ottawa Hospital, Ontario, ON, Canada. 8Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI), Ottawa, ON, Canada. 9School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. 10Faculty of Medicine, University of Versailles Saint-Quentin-enYvelines, Montigny-le-Bretonneux, France. 11Parc Sanitari Sant Joan de Dé u/CIBERSAM, Universitat de Barcelona, FundacióSant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain. 12Centre for Health, Performance, and Wellbeing, Anglia Ruskin University, Cambridge, UK. 13Department of Preventive Intervention for Psychiatric Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan. 14Stockholm Center for Health and Social Change (SCOHOST), Södertörn University, Huddinge, Sweden. 15Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada. 16Department of Psychiatry, University of Toronto, Toronto, ON, Canada. 17Pain and Rehabilitation Centre and Department of Health, Medicine and Caring Sciences, Linkoping University, Linkoping, Sweden. 18Department of Medicine, University of Cambridge, Cambridge, UK. 19ICREA, Pg. Lluis Companys 23, Barcelona, Spain. 20Centre of Chronic Illness and Ageing, University of Greenwich, London, UK. 21Suzanne Dworak-Peck School of Social Work, University of Southern California, Los Angeles, CA 90015, USA. 22Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK. 23Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK. 24Institute of Psychiatry and Mental Health. Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), CIBERSAM, Madrid, Spain. 25Imaging of Moodand Anxiety-Related Disorders (IMARD) Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, Barcelona, Spain. 26Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm, Sweden. 27Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy. 28OASIS service, South London and Maudsley NHS Foundation Trust, London, UK. 29National Institute of Health Research Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK. 30These authors contributed equally: Sojung Yoon, Sung Eun Kim.
*Corresponding author.
Abstract
Alzheimer’s disease (AD) results in progressive cognitive decline owing to the accumulation of amyloid plaques and hyperphosphorylated tau. MicroRNAs (miRNAs) have attracted attention as a putative diagnostic and therapeutic target for neurodegenerative diseases. However, existing meta-analyses on AD and its association with miRNAs have produced inconsistent results. The primary objective of this study is to evaluate the magnitude and consistency of differences in miRNA levels between AD patients, mild cognitive impairment (MCI) patients and healthy controls (HC). Articles investigating miRNA levels in blood, brain tissue, or cerebrospinal fluid (CSF) of AD and MCI patients versus HC were systematically searched in PubMed/Medline from inception to February 16th, 2021. Fixed- and random-effects meta-analyses were complemented with the I2 statistic to measure the heterogeneity, assessment of publication bias, sensitivity subgroup analyses (AD severity, brain region, post-mortem versus ante-mortem specimen for CSF and type of analysis used to quantify miRNA) and functional enrichment pathway analysis. Of the 1512 miRNAs included in 61 articles, 425 meta-analyses were performed on 334 miRNAs. Fifty-six miRNAs were significantly upregulated (n = 40) or downregulated (n = 16) in AD versus HC and all five miRNAs were significantly upregulated in MCI versus HC. Functional enrichment analysis confirmed that pathways related to apoptosis, immune response and inflammation were statistically enriched with upregulated pathways in participants with AD relative to HC. This study confirms that miRNAs’ expression is altered in AD and MCI compared to HC. These findings open new diagnostic and therapeutic perspectives for this disorder.
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