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The EMIF-AD Multimo...
The EMIF-AD Multimodal Biomarker Discovery study: design, methods and cohort characteristics
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Bos, I. (author)
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Vos, S. (author)
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Vandenberghe, R. (author)
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Scheltens, P. (author)
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Engelborghs, S. (author)
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Frisoni, G. (author)
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Molinuevo, J. L. (author)
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Wallin, A. (author)
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Lleo, A. (author)
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Popp, J. (author)
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Martinez-Lage, P. (author)
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Baird, A. (author)
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Dobson, R. (author)
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Legido-Quigley, C. (author)
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Sleegers, K. (author)
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Van Broeckhoven, C. (author)
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Bertram, L. (author)
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ten Kate, M. (author)
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Barkhof, F. (author)
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Lovestone, S. (author)
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Streffer, J. (author)
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Visser, P. J. (author)
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(creator_code:org_t)
- 2018-07-06
- 2018
- English.
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In: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 10
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https://alzres.biome...
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Abstract
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- Background: 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 (A beta) 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 A beta+ 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 e4 allele was more frequent amongst A beta+ 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). A beta+ 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 A beta and APOE epsilon 4 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Alzheimer's disease
- Biomarkers
- Multimodal
- Proteomics
- Genomics
- Metabolomics
- Plasma
- Magnetic resonance imaging
- DNA
- Cerebrospinal fluid
- cerebrospinal-fluid biomarkers
- mild cognitive impairment
- blood-based
- biomarkers
- alzheimers-disease
- csf biomarkers
- dementia
- atrophy
- diagnosis
- mri
- Neurosciences & Neurology
- khann g
- 1984
- neurology
- v34
- p939
- heltens p
- 1992
- journal of neurology neurosurgery and psychiatry
- v55
- p967
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Bos, I.
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Vos, S.
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Vandenberghe, R.
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Scheltens, P.
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Engelborghs, S.
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Frisoni, G.
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show more...
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Molinuevo, J. L.
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Wallin, A.
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Lleo, A.
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Popp, J.
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Martinez-Lage, P ...
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Baird, A.
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Dobson, R.
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Legido-Quigley, ...
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Sleegers, K.
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Van Broeckhoven, ...
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Bertram, L.
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ten Kate, M.
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Barkhof, F.
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Zetterberg, Henr ...
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Lovestone, S.
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Streffer, J.
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Visser, P. J.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Alzheimers Resea ...
- By the university
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University of Gothenburg