The EMIF-AD Multimodal Biomarker Discovery study : Design, methods and cohort characteristics
Bos, Isabelle (Maastricht University)
Vos, Stephanie (Maastricht University)
Vandenberghe, Rik (Katholieke Universiteit Leuven)
Scheltens, Philip (Amsterdam UMC. University Medical Center)
Engelborghs, Sebastiaan (University of Antwerp)
Frisoni, Giovanni (IRCCS Instituto Centro San Giovanni di Dio Fatebenefratelli)
Molinuevo, José Luis (Fundació Pasqual Maragall)
Wallin, Anders (Institute of Neuroscience and Physiology)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Popp, Julius (Lausanne University Hospital)
Martinez-Lage, Pablo (Centro de Investigación y Tecnología Agroalimentaria de Aragón)
Baird, Alison (University of Oxford)
Dobson, Richard (NIHR University College London Hospitals)
Legido-Quigley, Cristina (King's College London)
Sleegers, Kristel (University of Antwerp)
Van Broeckhoven, Christine (University of Antwerp)
Bertram, Lars (University of Oslo)
Ten Kate, Mara (Amsterdam UMC. University Medical Center)
Barkhof, Frederik (Amsterdam UMC. University Medical Center)
Zetterberg, Henrik (UK Dementia Research Institute)
Lovestone, Simon (University of Oxford)
Streffer, Johannes (Janssen Pharmaceutical Companies)
Visser, Pieter Jelle (Vrije Universiteit Amsterdam)
Universitat Autònoma de Barcelona

Data:	2018
Resum:	There is an urgent need for novel, noninvasive biomarkers to diagnose Alzheimer's disease (AD) in the predementia stages and to predict the rate of decline. Therefore, we set up the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study. In this report we describe the design of the study, the methods used and the characteristics of the participants. Participants were selected from existing prospective multicenter and single-center European studies. Inclusion criteria were having normal cognition (NC) or a diagnosis of mild cognitive impairment (MCI) or AD-type dementia at baseline, age above 50 years, known amyloid-beta (Aβ) status, availability of cognitive test results and at least two of the following materials: plasma, DNA, magnetic resonance imaging (MRI) or cerebrospinal fluid (CSF). Targeted and untargeted metabolomic and proteomic analyses were performed in plasma, and targeted and untargeted proteomics were performed in CSF. Genome-wide SNP genotyping, next-generation sequencing and methylation profiling were conducted in DNA. Visual rating and volumetric measures were assessed on MRI. Baseline characteristics were analyzed using ANOVA or chi-square, rate of decline analyzed by linear mixed modeling. We included 1221 individuals (NC n = 492, MCI n = 527, AD-type dementia n = 202) with a mean age of 67. 9 (SD 8. 3) years. The percentage Aβ+ was 26% in the NC, 58% in the MCI, and 87% in the AD-type dementia groups. Plasma samples were available for 1189 (97%) subjects, DNA samples for 929 (76%) subjects, MRI scans for 862 (71%) subjects and CSF samples for 767 (63%) subjects. For 759 (62%) individuals, clinical follow-up data were available. In each diagnostic group, the APOE ϵ4 allele was more frequent amongst Aβ+ individuals (p < 0. 001). Only in MCI was there a difference in baseline Mini Mental State Examination (MMSE) score between the A groups (p < 0. 001). Aβ+ had a faster rate of decline on the MMSE during follow-up in the NC (p < 0. 001) and MCI (p < 0. 001) groups. The characteristics of this large cohort of elderly subjects at various cognitive stages confirm the central roles of Aβ and APOE ϵ4 in AD pathogenesis. The results of the multimodal analyses will provide new insights into underlying mechanisms and facilitate the discovery of new diagnostic and prognostic AD biomarkers. All researchers can apply for access to the EMIF-AD MBD data by submitting a research proposal via the EMIF-AD Catalog.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alzheimer's disease ; Biomarkers ; Cerebrospinal fluid ; DNA ; Genomics ; Magnetic resonance imaging ; Metabolomics ; Multimodal ; Plasma ; Proteomics
Publicat a:	Alzheimer's research & therapy, Vol. 10 Núm. 1 (june 2018) , p. 64, ISSN 1758-9193

DOI: 10.1186/s13195-018-0396-5
PMID: 29980228

9 p, 745.8 KB

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