Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology.

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Shi, LiuDepartment of Psychiatry, University of Oxford, UK (author)

Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology.

Article/chapterEnglish2020

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IOS Press,2020

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LIBRIS-ID:oai:gup.ub.gu.se/295674
https://gup.ub.gu.se/publication/295674URI
https://doi.org/10.3233/JAD-200208DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-85111URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:145020231URI

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Language:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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Funding Agencies:Innovative Medicines Initiative Joint Undertaking under EMIF from the European Union's Seventh Framework Programme (FP7/2007-2013) 115372EFPIA companies' European CommissionEuropean Commission Joint Research CentreEuropean Union (EU) QLRT-20012455 37670Stichting voor Alzheimer Onderzoek 11020 13007 15005Swiss National Science Foundation (SNSF) SNF 320030 141179Department of Health of the Basque Government 17.0.1.08.12.0000.2.454.01.41142.001.HUniversity of Antwerp Research Fund NIHR biomedical research centre at UCLH Health Data Research UK National Institute for Health Research (NIHR)Maudsley NHS Foundation Trust King's College London NIHR University College London Hospitals Biomedical Research Centre DPUK through MRC MR/L023784/2Medical Research Council UK (MRC) MC PC 17215NIHR Biomedical Research Centre at Oxford Health NHS Foundation Trust
Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown.We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes.We first overexpressed DKK1 in HEK293A cells and quantified 1,128 proteins in cell lysates using aptamer capture arrays (SomaScan) to obtain a protein signature induced by DKK1. We then used the same assay to measure the DKK1-signature proteins in human plasma in two large cohorts, EMIF (n = 785) and ANM (n = 677).We identified a 100-protein signature induced by DKK1 in vitro. Subsets of proteins, along with age and apolipoprotein E ɛ4 genotype distinguished amyloid pathology (A + T-N-, A+T+N-, A+T-N+, and A+T+N+) from no AD pathology (A-T-N-) with an area under the curve of 0.72, 0.81, 0.88, and 0.85, respectively. Furthermore, we found that some signature proteins (e.g., Complement C3 and albumin) were associated with cognitive score and AD diagnosis in both cohorts.Our results add further evidence for a role of DKK regulation of Wnt signaling in AD and suggest that DKK1 induced signature proteins obtained in vitro could reflect theATNframework as well as predict disease severity and progression in vivo.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinsk bioteknologi Medicinsk bioteknologi hsv//swe
MEDICAL AND HEALTH SCIENCES Medical Biotechnology Medical Biotechnology hsv//eng
ATN framework

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Winchester, Laura M (author)
Liu, Benjamine Y (author)
Killick, Richard (author)
Ribe, Elena M (author)
Westwood, Sarah (author)
Baird, Alison L (author)
Buckley, Noel J (author)
Hong, Shengjun (author)
Dobricic, Valerija (author)
Kilpert, Fabian (author)
Franke, Andre (author)
Kiddle, Steven (author)
Sattlecker, Martina (author)
Dobson, Richard (author)
Cuadrado, Antonio (author)
Hye, Abdul (author)
Ashton, Nicholas J.Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xashtn (author)
Morgan, Angharad R (author)
Bos, Isabelle (author)
Vos, Stephanie J B (author)
Ten Kate, Mara (author)
Scheltens, Philip (author)
Vandenberghe, Rik (author)
Gabel, Silvy (author)
Meersmans, Karen (author)
Engelborghs, Sebastiaan (author)
De Roeck, Ellen E (author)
Sleegers, Kristel (author)
Frisoni, Giovanni B (author)
Blin, Olivier (author)
Richardson, Jill C (author)
Bordet, Régis (author)
Molinuevo, José L (author)
Rami, Lorena (author)
Wallin, Anders,1950Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xwaand (author)
Kettunen, PetronellaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xketpe (author)
Tsolaki, Magda (author)
Verhey, Frans (author)
Lleó, Alberto (author)
Alcolea, Daniel (author)
Popp, JuliusKarolinska Institutet (author)
Peyratout, Gwendoline (author)
Martinez-Lage, Pablo (author)
Tainta, Mikel (author)
Johannsen, Peter (author)
Teunissen, Charlotte E (author)
Freund-Levi, Yvonne,1956-Örebro universitet,Institutionen för medicinska vetenskaper,Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden; Department of Old Age Psychiatry, Psychology and Neuroscience, King's College London, UK; Department of Psychiatry, Örebro Universitetssjukhus, Örebro, Sweden(Swepub:oru)yfi (author)
Frölich, Lutz (author)
Legido-Quigley, Cristina (author)
Barkhof, Frederik (author)
Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbleka (author)
Rasmussen, Katrine Laura (author)
Nordestgaard, Børge Grønne (author)
Frikke-Schmidt, Ruth (author)
Nielsen, Sune Fallgaard (author)
Soininen, Hilkka (author)
Vellas, Bruno (author)
Kloszewska, Iwona (author)
Mecocci, Patrizia (author)
Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe (author)
Morgan, B Paul (author)
Streffer, Johannes (author)
Visser, Pieter Jelle (author)
Bertram, Lars (author)
Nevado-Holgado, Alejo J (author)
Lovestone, SimonDepartment of Psychiatry, University of Oxford, UK (author)
Department of Psychiatry, University of Oxford, UKInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

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In:Journal of Alzheimer's disease : JAD: IOS Press77:3, s. 1353-13681875-89081387-2877

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By the author/editor: Shi, Liu; Winchester, Laur ...; Liu, Benjamine Y; Killick, Richard; Ribe, Elena M; Westwood, Sarah; show more...; Baird, Alison L; Buckley, Noel J; Hong, Shengjun; Dobricic, Valeri ...; Kilpert, Fabian; Franke, Andre; Kiddle, Steven; Sattlecker, Mart ...; Dobson, Richard; Cuadrado, Antoni ...; Hye, Abdul; Ashton, Nicholas ...; Morgan, Angharad ...; Bos, Isabelle; Vos, Stephanie J ...; Ten Kate, Mara; Scheltens, Phili ...; Vandenberghe, Ri ...; Gabel, Silvy; Meersmans, Karen; Engelborghs, Seb ...; De Roeck, Ellen ...; Sleegers, Kriste ...; Frisoni, Giovann ...; Blin, Olivier; Richardson, Jill ...; Bordet, Régis; Molinuevo, José ...; Rami, Lorena; Wallin, Anders, ...; Kettunen, Petron ...; Tsolaki, Magda; Verhey, Frans; Lleó, Alberto; Alcolea, Daniel; Popp, Julius; Peyratout, Gwend ...; Martinez-Lage, P ...; Tainta, Mikel; Johannsen, Peter; Teunissen, Charl ...; Freund-Levi, Yvo ...; Frölich, Lutz; Legido-Quigley, ...; Barkhof, Frederi ...; Blennow, Kaj, 19 ...; Rasmussen, Katri ...; Nordestgaard, Bø ...; Frikke-Schmidt, ...; Nielsen, Sune Fa ...; Soininen, Hilkka; Vellas, Bruno; Kloszewska, Iwon ...; Mecocci, Patrizi ...; Zetterberg, Henr ...; Morgan, B Paul; Streffer, Johann ...; Visser, Pieter J ...; Bertram, Lars; Nevado-Holgado, ...; Lovestone, Simon; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

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