{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:16:19Z","timestamp":1777396579567,"version":"3.51.4"},"reference-count":46,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2020,9,29]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer\u2019s disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We identified a 100-protein signature induced by DKK1 in vitro. Subsets of proteins, along with age and apolipoprotein E \u025b4 genotype distinguished amyloid pathology (A + T\u2013N\u2013, A+T+N\u2013, A+T\u2013N+, and A+T+N+) from no AD pathology (A\u2013T\u2013N\u2013) 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-200208","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T13:56:14Z","timestamp":1598018174000},"page":"1353-1368","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Dickkopf-1 Overexpression\n                    <i>in vitro<\/i>\n                    Nominates Candidate Blood Biomarkers Relating to Alzheimer\u2019s Disease Pathology"],"prefix":"10.1177","volume":"77","author":[{"given":"Liu","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura M.","family":"Winchester","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamine Y.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Killick","sequence":"additional","affiliation":[{"name":"King\u2019s College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena M.","family":"Ribe","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Westwood","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison L.","family":"Baird","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noel J.","family":"Buckley","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengjun","family":"Hong","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerija","family":"Dobricic","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian","family":"Kilpert","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre","family":"Franke","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Kiddle","sequence":"additional","affiliation":[{"name":"King\u2019s College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK"},{"name":"MRC Social, Genetic and Developmental Psychiatry Centre, King\u2019s College London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Sattlecker","sequence":"additional","affiliation":[{"name":"King\u2019s College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, London, UK"},{"name":"MRC Social, Genetic and Developmental Psychiatry Centre, King\u2019s College London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Dobson","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK"},{"name":"Institute of Health Informatics, University College London, London, 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