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dc.contributor.authorBos, Isabelle
dc.contributor.authorVos, Stephanie
dc.contributor.authorVandenberghe, Rik
dc.contributor.authorScheltens, Philip
dc.contributor.authorEngelborghs, Sebastiaan
dc.contributor.authorFrisoni, Giovanni
dc.contributor.authorMolinuevo, José L
dc.contributor.authorWallin, Anders
dc.contributor.authorLleó, Alberto
dc.contributor.authorPopp, Julius
dc.contributor.authorMartinez-Lage, Pablo
dc.contributor.authorBaird, Alison
dc.contributor.authorDobson, Richard
dc.contributor.authorLegido-Quigley, Cristina
dc.contributor.authorSleegers, Kristel
dc.contributor.authorVan Broeckhoven, Christine
dc.contributor.authorBertram, Lars
dc.contributor.authorten Kate, Mara
dc.contributor.authorBarkhof, Frederik
dc.contributor.authorZetterberg, Henrik
dc.contributor.authorLovestone, Simon
dc.contributor.authorStreffer, Johannes
dc.contributor.authorVisser, Pieter J
dc.date.accessioned2018-07-10T07:56:14Z
dc.date.available2018-07-10T07:56:14Z
dc.date.issued2018
dc.identifier.citationAlzheimer's Research & Therapy. 2018 Jul 06;10(1):64
dc.identifier.urihttp://hdl.handle.net/10852/62181
dc.description.abstractBackground 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. Methods 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. Results 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. Conclusions 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.
dc.language.isoeng
dc.rightsThe Author(s); licensee BioMed Central Ltd.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleThe EMIF-AD Multimodal Biomarker Discovery study: design, methods and cohort characteristics
dc.typeJournal article
dc.date.updated2018-07-10T07:56:16Z
dc.creator.authorBos, Isabelle
dc.creator.authorVos, Stephanie
dc.creator.authorVandenberghe, Rik
dc.creator.authorScheltens, Philip
dc.creator.authorEngelborghs, Sebastiaan
dc.creator.authorFrisoni, Giovanni
dc.creator.authorMolinuevo, José L
dc.creator.authorWallin, Anders
dc.creator.authorLleó, Alberto
dc.creator.authorPopp, Julius
dc.creator.authorMartinez-Lage, Pablo
dc.creator.authorBaird, Alison
dc.creator.authorDobson, Richard
dc.creator.authorLegido-Quigley, Cristina
dc.creator.authorSleegers, Kristel
dc.creator.authorVan Broeckhoven, Christine
dc.creator.authorBertram, Lars
dc.creator.authorten Kate, Mara
dc.creator.authorBarkhof, Frederik
dc.creator.authorZetterberg, Henrik
dc.creator.authorLovestone, Simon
dc.creator.authorStreffer, Johannes
dc.creator.authorVisser, Pieter J
dc.identifier.doihttps://doi.org/10.1186/s13195-018-0396-5
dc.identifier.urnURN:NBN:no-64773
dc.type.documentTidsskriftartikkel
dc.type.peerreviewedPeer reviewed
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/62181/1/13195_2018_Article_396.pdf
dc.type.versionPublishedVersion
cristin.articleid64


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