Multiomics integrative analysis identifies APOE allele-specific blood biomarkers associated to Alzheimer's disease etiopathogenesis.

Autor:	Madrid L; Andalusion Bioiformatics Research Centre (CAEBi), Sevilla, Spain., Moreno-Grau S; Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain., Ahmad S; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands., González-Pérez A; Andalusion Bioiformatics Research Centre (CAEBi), Sevilla, Spain., de Rojas I; Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain., Xia R; Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Martino Adami PV; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, Cologne, Germany., García-González P; Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain., Kleineidam L; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, Cologne, Germany.; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany., Yang Q; Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA., Damotte V; University Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque Et Déterminants Moléculaires des Maladies Liées au Vieillissement, Lille, France., Bis JC; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Noguera-Perea F; Unidad de Demencias, Hospital Clínico Universitario Virgen de la Arrixaca, Carretera de Madrid-Cartagena s/n, 30120 El Palmar, Murcia, España., Bellenguez C; University Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque Et Déterminants Moléculaires des Maladies Liées au Vieillissement, Lille, France., Jian X; Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Marín-Muñoz J; Unidad de Demencias, Hospital Clínico Universitario Virgen de la Arrixaca, Carretera de Madrid-Cartagena s/n, 30120 El Palmar, Murcia, España., Grenier-Boley B; University Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque Et Déterminants Moléculaires des Maladies Liées au Vieillissement, Lille, France., Orellana A; Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain., Ikram MA; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands., Amouyel P; University Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque Et Déterminants Moléculaires des Maladies Liées au Vieillissement, Lille, France., Satizabal CL; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX 78229, USA.; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA., Real LM; Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Sevilla, Spain.; Department of Surgery, Biochemistry and Immunology, University of Malaga, Spain., Antúnez-Almagro C; Unidad de Demencias, Hospital Clínico Universitario Virgen de la Arrixaca, Carretera de Madrid-Cartagena s/n, 30120 El Palmar, Murcia, España., DeStefano A; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA., Cabrera-Socorro A; Janssen Research and Development, a Division of Janssen Pharmaceutica N.V., Beerse, Belgium., Sims R; Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK., Van Duijn CM; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands., Boerwinkle E; Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Ramírez A; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, Cologne, Germany.; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany., Fornage M; Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Lambert JC; University Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque Et Déterminants Moléculaires des Maladies Liées au Vieillissement, Lille, France., Williams J; Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK.; UKDRI@Cardiff, School of Medicine, Cardiff University, Cardiff, UK., Seshadri S; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX 78229, USA.; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA., Ried JS; AbbVie Deutschland GmbH & Co. KG, Genomics Research Center, Knollstrasse, Ludwigshafen, Germany., Ruiz A; Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain., Saez ME; Andalusion Bioiformatics Research Centre (CAEBi), Sevilla, Spain.
Jazyk:	angličtina
Zdroj:	Aging [Aging (Albany NY)] 2021 Apr 12; Vol. 13 (7), pp. 9277-9329. Date of Electronic Publication: 2021 Apr 12.
DOI:	10.18632/aging.202950
Abstrakt:	Alzheimer's disease (AD) is the most common form of dementia, currently affecting 35 million people worldwide. Apolipoprotein E (APOE) ε4 allele is the major risk factor for sporadic, late-onset AD (LOAD), which comprises over 95% of AD cases, increasing the risk of AD 4-12 fold. Despite this, the role of APOE in AD pathogenesis is still a mystery. Aiming for a better understanding of APOE-specific effects, the ADAPTED consortium analysed and integrated publicly available data of multiple OMICS technologies from both plasma and brain stratified by APOE haplotype ( APOE2, APOE3 and APOE4 ). Combining genome-wide association studies (GWAS) with differential mRNA and protein expression analyses and single-nuclei transcriptomics, we identified genes and pathways contributing to AD in both APOE dependent and independent fashion. Interestingly, we characterised a set of biomarkers showing plasma and brain consistent protein profiles and opposite trends in APOE2 and APOE4 AD cases that could constitute screening tools for a disease that lacks specific blood biomarkers. Beside the identification of APOE-specific signatures, our findings advocate that this novel approach, based on the concordance across OMIC layers and tissues, is an effective strategy for overcoming the limitations of often underpowered single-OMICS studies.
Databáze:	MEDLINE
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