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

Shi, Liu (author)
Department of Psychiatry, University of Oxford, UK
Winchester, Laura M (author)
Liu, Benjamine Y (author)
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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. (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
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, 1950 (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
Kettunen, Petronella (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
Tsolaki, Magda (author)
Verhey, Frans (author)
Lleó, Alberto (author)
Alcolea, Daniel (author)
Popp, Julius (author)
Karolinska Institutet
Peyratout, Gwendoline (author)
Martinez-Lage, Pablo (author)
Tainta, Mikel (author)
Johannsen, Peter (author)
Teunissen, Charlotte E (author)
Freund-Levi, Yvonne, 1956- (author)
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
Frölich, Lutz (author)
Legido-Quigley, Cristina (author)
Barkhof, Frederik (author)
Blennow, Kaj, 1958 (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
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, 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
Morgan, B Paul (author)
Streffer, Johannes (author)
Visser, Pieter Jelle (author)
Bertram, Lars (author)
Nevado-Holgado, Alejo J (author)
Lovestone, Simon (author)
Department of Psychiatry, University of Oxford, UK
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 (creator_code:org_t)
IOS Press, 2020
2020
English.
In: Journal of Alzheimer's disease : JAD. - : IOS Press. - 1875-8908 .- 1387-2877. ; 77:3, s. 1353-1368
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • 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

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical 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  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

Keyword

ATN framework

Publication and Content Type

ref (subject category)
art (subject category)

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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...
About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Neurosciences
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Medical Biotechn ...
and Medical Biotechn ...
Articles in the publication
Journal of Alzhe ...
By the university
University of Gothenburg
Örebro University
Karolinska Institutet

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