Plasma Proteomic Biomarkers Relating to Alzheimer's Disease : A Meta-Analysis Based on Our Own Studies
Shi, L. (Department of Psychiatry. University of Oxford)
Buckley, Noel J (Department of Psychiatry. University of Oxford)
Bos, Isabelle (Alzheimer Center. VU University Medical Center)
Engelborghs, Sebastiaan (Department of Neurology. Universitair Ziekenhuis Brussel. Center for Neurociences (C4N). Vrije Universiteit Brussel)
Sleegers, Kristel (Institute Born-Bunge. Department of Biomedical Sciences. University of Antwerp)
Frisoni, Giovanni B. (University of Geneva. Department of Psychiatry)
Wallin, Anders (Institute of Neuroscience and Physiology. Department of Psychiatry and Neurochemistry. The Sahlgrenska Academy at the University of Gothenburg)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Popp, J. (Geriatric Psychiatry. Department of Mental Health and Psychiatry. Geneva University Hospitals)
Martinez-Lage, P. (CITA-Alzheimer Foundation)
Legido-Quigley, Cristina (The Systems Medicine Group. Steno Diabetes Center)
Barkhof, Frederik (UCL Institutes of Neurology and Healthcare Engineering)
Zetterberg, Henrik (Department of Neurodegenerative Disease. UCL Institute of Neurology)
Visser, P.J. (Alzheimer Center. VU University Medical Center)
Bertram, Lars (Department of Psychology. University of Oslo)
Lovestone, S.
Nevado-Holgado, Alejo (Department of Psychiatry. University of Oxford)

Data:	2021
Resum:	Background and Objective: Plasma biomarkers for the diagnosis and stratification of Alzheimer's disease (AD) are intensively sought. However, no plasma markers are well established so far for AD diagnosis. Our group has identified and validated various blood-based proteomic biomarkers relating to AD pathology in multiple cohorts. The study aims to conduct a meta-analysis based on our own studies to systematically assess the diagnostic performance of our previously identified blood biomarkers. Methods: To do this, we included seven studies that our group has conducted during the last decade. These studies used either Luminex xMAP or ELISA to measure proteomic biomarkers. As proteins measured in these studies differed, we selected protein based on the criteria that it must be measured in at least four studies. We then examined biomarker performance using random-effect meta-analyses based on the mean difference between biomarker concentrations in AD and controls (CTL), AD and mild cognitive impairment (MCI), MCI, and CTL as well as MCI converted to dementia (MCIc) and non-converted (MCInc) individuals. Results: An overall of 2,879 subjects were retrieved for meta-analysis including 1,053 CTL, 895 MCI, 882 AD, and 49 frontotemporal dementia (FTD) patients. Six proteins were measured in at least four studies and were chosen for meta-analyses for AD diagnosis. Of them, three proteins had significant difference between AD and controls, among which alpha-2-macroglobulin (A2M) and ficolin-2 (FCN2) increased in AD while fibrinogen gamma chain (FGG) decreased in AD compared to CTL. Furthermore, FGG significantly increased in FTD compared to AD. None of the proteins passed the significance between AD and MCI, or MCI and CTL, or MCIc and MCInc, although complement component 4 (CC4) tended to increase in MCIc individuals compared to MCInc. Conclusions: The results suggest that A2M, FCN2, and FGG are promising biomarkers to discriminate AD patients from controls, which are worthy of further validation.
Ajuts:	European Commission 37670
Nota:	Altres ajuts: Innovative Medicines Initiative Joint Undertaking (EMIF grant agreement no. 115372); Department of Health of the Basque Government (allocation 17.0.1.08.12.0000.2.454.01.41142.001.H); University of Antwerp Research Fund. European Comission. Seventh Framework Programme FP7/2007-2013 and European Comission. Fifth Framework Programme QLRT2001-2455
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 (AD) ; Diagnosis ; Blood biomarkers ; Meta-analysis ; Proteomic
Publicat a:	Frontiers in aging neuroscience, Vol. 13 (July 2021) , p. 712545, ISSN 1663-4365

DOI: 10.3389/fnagi.2021.712545
PMID: 34366831

8 p, 1.7 MB

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