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Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay
- Source :
- Alzheimer's & Dementia, Vol. 15, No 11 (2019) pp. 1478-1488, Alzheimer's & Dementia, Alzheimer's & Dementia : the Journal of the Alzheimer's Association, Alzheimer's & Dementia : the Journal of the Alzheimer's Association, 2019, 15 (11), pp.1478-1488. ⟨10.1016/j.jalz.2019.06.4951⟩, Alzheimer's & dementia, Alzheimer's and Dementia, 15(11), 1478-1488. Elsevier, Alzheimers & Dementia, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, Shi, L, Westwood, S, Baird, A L, Winchester, L, Dobricic, V, Kilpert, F, Hong, S, Franke, A, Hye, A, Ashton, N J, Morgan, A R, Bos, I, Vos, S J B, Buckley, N J, Kate, M T, Scheltens, P, Vandenberghe, R, Gabel, S, Meersmans, K, Engelborghs, S, de Roeck, E E, Sleegers, K, Frisoni, G B, Blin, O, Richardson, J C, Bordet, R G, Molinuevo, J L, Rami, L, Wallin, A, Kettunen, P, Tsolaki, M, Verhey, F, Lleó, A, Alcolea, D, Popp, J, Peyratout, G, Martinez-Lage, P, Tainta, M, Johannsen, P, Teunissen, C E, Freund-Levi, Y, Frölich, L, Legido-Quigley, C, Barkhof, F, Blennow, K, Zetterberg, H, Baker, S, Morgan, B P, Streffer, J, Visser, P J, Bertram, L, Lovestone, S & Nevado-Holgado, A J 2019, ' Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay ', Alzheimer's and Dementia, vol. 15, no. 11, pp. 1478-1488 . https://doi.org/10.1016/j.jalz.2019.06.4951, Alzheimer's & dementia, vol. 15, no. 11, pp. 1478-1488, Alzheimer's & Dementia, 15(11), 1478-1488. Elsevier Science
- Publication Year :
- 2019
-
Abstract
- Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted to specific proteins or are biased toward high abundant proteins. 4001 plasma proteins were measured in two groups of participants (discovery group = 516, replication group = 365) selected from the European Medical Information Framework for Alzheimer's disease Multimodal Biomarker Discovery study, all of whom had measures of amyloid. A panel of proteins (n = 44), along with age and apolipoprotein E (APOE) ε4, predicted brain amyloid deposition with good performance in both the discovery group (area under the curve = 0.78) and the replication group (area under the curve = 0.68). Furthermore, a causal relationship between amyloid and tau was confirmed by Mendelian randomization. The results suggest that high-dimensional plasma protein testing could be a useful and reproducible approach for measuring brain amyloid deposition. This research was conducted as part of the EMIF-AD project, which has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Program (FP7/2007-2013), and EFPIA companies’ in-kind contribution. The DESCRIPA study was funded by the European Commission within the 5th framework program (QLRT-2001-2455). The EDAR study was funded by the European Commission within the 5th framework program (contract # 37670). The Leuven cohort was funded by the Stichting voor Alzheimer Onderzoek (grant numbers #11020, #13007, and #15005). R.V. is a senior clinical investigator of the Flemish Research Foundation (FWO). J.S. is currently an employee of UCB, Braine-l’Alleud, Belgium. The San Sebastian GAP study is partially funded by the Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H). The authors acknowledge the contribution of the personnel of the Genomic Service Facility at the VIB-U Antwerp Center for Molecular Neurology. The research at VIBCMN is funded in part by the University of Antwerp Research Fund. F.B. is supported by the NIHR biomedical research centre at UCLH. L.S. is funded by DPUK through MRC (grant no. MR/L023784/2) and the UK Medical Research Council Award to the University of Oxford (grant no. MC_PC_17215).
- Subjects :
- 0301 basic medicine
Apolipoprotein E
Male
Proteomics
Neurology
Epidemiology
Apolipoprotein E4
Disease
SOMAscan assay
ddc:616.89
BLOOD-BASED BIOMARKERS
0302 clinical medicine
CASCADE HYPOTHESIS
MARKERS
Tau
Medicine
Biomarker discovery
DRUG
Medicine(all)
Health Policy
Age Factors
Brain
Middle Aged
Blood proteins
3. Good health
Europe
ALZHEIMERS-DISEASE
Psychiatry and Mental health
MENDELIAN RANDOMIZATION
Biomarker (medicine)
Female
Life Sciences & Biomedicine
medicine.medical_specialty
Amyloid
MODELS
Clinical Neurology
Replication
Plasma proteomics
Computational biology
Article
SIGNALING PATHWAYS
03 medical and health sciences
Cellular and Molecular Neuroscience
AGE
Developmental Neuroscience
Alzheimer Disease
Amyloid β
Causal relationship
Mendelian randomization
Humans
Biology
Aged
Science & Technology
business.industry
[SCCO.NEUR]Cognitive science/Neuroscience
Amyloid beta
030104 developmental biology
Neurology (clinical)
Human medicine
Neurosciences & Neurology
Geriatrics and Gerontology
TAU
business
030217 neurology & neurosurgery
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 15525260 and 15525279
- Volume :
- 15
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Alzheimer's and Dementia
- Accession number :
- edsair.doi.dedup.....f48aedf4ff7af033c32b127dfc1bff16