Autor: |
Isabelle Bos, Stephanie Vos, Rik Vandenberghe, Philip Scheltens, Sebastiaan Engelborghs, Giovanni Frisoni, José Luis Molinuevo, Anders Wallin, Alberto Lleó, Julius Popp, Pablo Martinez-Lage, Alison Baird, Richard Dobson, Cristina Legido-Quigley, Kristel Sleegers, Christine Van Broeckhoven, Lars Bertram, Mara ten Kate, Frederik Barkhof, Henrik Zetterberg, Simon Lovestone, Johannes Streffer, Pieter Jelle Visser |
Jazyk: |
angličtina |
Rok vydání: |
2018 |
Předmět: |
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Zdroj: |
Alzheimer’s Research & Therapy, Vol 10, Iss 1, Pp 1-9 (2018) |
Druh dokumentu: |
article |
ISSN: |
1758-9193 |
DOI: |
10.1186/s13195-018-0396-5 |
Popis: |
Abstract 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 (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 |
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