Evidence map›Paper›PMID 32831200›Full record

ArticleJournal of Alzheimer's disease : JAD2020

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

Liu Shi, Laura M Winchester, Benjamine Y Liu, Richard Killick, Elena M Ribe, Sarah Westwood, Alison L Baird, Noel J Buckley, Shengjun Hong, Valerija Dobricic and 57 more

Open access · bronzeAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

67 authors at 20 institutions in 16 countries.

Liu ShiDepartment of Psychiatry, University of Oxford, UK.
Laura M WinchesterDepartment of Psychiatry, University of Oxford, UK.
Benjamine Y LiuDepartment of Psychiatry, University of Oxford, UK.
Richard KillickKing's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK.
Elena M RibeDepartment of Psychiatry, University of Oxford, UK.
Sarah WestwoodDepartment of Psychiatry, University of Oxford, UK.
Alison L BairdDepartment of Psychiatry, University of Oxford, UK.
Noel J BuckleyDepartment of Psychiatry, University of Oxford, UK.
Shengjun HongLübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany.
Valerija DobricicLübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany.
Fabian KilpertLübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany.
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Steven KiddleKing's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK.
Martina SattleckerKing's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK.
Richard DobsonDepartment of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Antonio CuadradoCentro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Investigación Sanitaria La Paz (IdiPaz), Instituto de Investigaciones Biomédicas Alberto Sols UAM-CSIC, and Department of Biochemistry, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain.
Abdul HyeKing's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK.
Nicholas J AshtonKing's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK.
Angharad R MorganDementia Research Institute Cardiff, Cardiff University, Cardiff, UK.
Isabelle BosDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Stephanie J B VosDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Mara Ten KateAlzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
Philip ScheltensAlzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
Rik VandenbergheUniversity Hospital Leuven, Leuven, Belgium.
Silvy GabelUniversity Hospital Leuven, Leuven, Belgium.
Karen MeersmansUniversity Hospital Leuven, Leuven, Belgium.
Sebastiaan EngelborghsCenter for Neurosciences, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Ellen E De RoeckCenter for Neurosciences, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Kristel SleegersInstitute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Giovanni B FrisoniUniversity of Geneva, Geneva, Switzerland.
Olivier BlinAIX Marseille University, INS, Ap-hm, Marseille, France.
Jill C RichardsonNeurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK.
Régis BordetUniversity of Lille, Inserm, CHU Lille, France.
José L MolinuevoAlzheimer's disease & other cognitive disorders unit, Hospital Clínic, Barcelona, Spain.
Lorena RamiBarcelonaBeta Brain Research Center, Universitat Pompeu Fabra, Barcelona, Spain.
Anders WallinDepartment of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Petronella KettunenDepartment of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Magda Tsolaki1st Department of Neurology, AHEPA University Hospital, school of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Makedonia, Greece.
Frans VerheyDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Alberto LleóDepartment of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Daniel AlcoleaDepartment of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Julius PoppDepartment of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
Gwendoline PeyratoutDepartment of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
Pablo Martinez-LageCITA-Alzheimer Foundation, San Sebastian, Spain.
Mikel TaintaCITA-Alzheimer Foundation, San Sebastian, Spain.
Peter JohannsenDanish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Charlotte E TeunissenNeurochemistry Laboratory, dept of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, the Netherlands.
Yvonne Freund-LeviSchool of Medical Sciences, Örebro University, Örebro, Sweden.
Lutz FrölichDepartment of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
Cristina Legido-QuigleyKings College London, London, UK.
Frederik BarkhofDepartment of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherland.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Katrine Laura RasmussenDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Børge Grønne NordestgaardThe Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Ruth Frikke-SchmidtDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Sune Fallgaard NielsenThe Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Hilkka SoininenNeurology / Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Bruno VellasToulouse Gerontopole University Hospital, Univeriste Paul Sabatier, INSERM U 558, France.
Iwona KloszewskaMedical University of Lodz, Lodz, Poland.
Patrizia MecocciSection of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
B Paul MorganDementia Research Institute Cardiff, Cardiff University, Cardiff, UK.
Johannes StrefferDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Pieter Jelle VisserDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
Lars BertramLübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany.
Alejo J Nevado-HolgadoDepartment of Psychiatry, University of Oxford, UK.
Simon LovestoneDepartment of Psychiatry, University of Oxford, UK.
University of Oxford · GBKing's College London · GBUniversity of Copenhagen · DKMaastricht University · NLSahlgrenska University Hospital · SEUniversity of Lübeck · DEAmsterdam UMC Location Vrije Universiteit Amsterdam · NLHospital de Sant Pau · ESKU Leuven · BEUK Dementia Research Institute · GBUniversitat Pompeu Fabra · ESUniversity of Geneva · CHVrije Universiteit Brussel · BEAix-Marseille Université · FRAmsterdam Neuroscience · NLAristotle University of Thessaloniki · GRBiomedical Research Networking Center on Neurodegenerative Diseases · ESChristian-Albrechts-Universität zu Kiel · DECopenhagen University Hospital · DKFundacion CITA Alzheimer · ES

Funding

Department of HealthMedical Research Council MC_PC_17214Medical Research Council MC_PC_17215Medical Research Council MR/L011859/1Medical Research Council MR/L023784/2
6 · The paper itself

Abstract

backgroundPrevious 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.

objectiveWe 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.

methodsWe 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).

resultsWe 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.

conclusionsOur 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.

Indexed as

AgedAlzheimer DiseaseBiomarkersFemaleGene ExpressionHEK293 CellsHumansIntercellular Signaling Peptides and ProteinsMaleMiddle AgedBiomarkersDKK1 protein, humanIntercellular Signaling Peptides and ProteinsATN frameworkDickkopf-1replicationSomaScanWnt signaling

Identifiers

PMID32831200
PMCPMC7683080
OpenAlexW3081054827

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.