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

Details

Serval ID
serval:BIB_F14D1CF79B2B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology
Journal
Journal of Alzheimer's Disease
Author(s)
Shi Liu, Winchester Laura M., Liu Benjamine Y., Killick Richard, Ribe Elena M., Westwood Sarah, Baird Alison L., Buckley Noel J., Hong Shengjun, Dobricic Valerija, Kilpert Fabian, Franke Andre, Kiddle Steven, Sattlecker Martina, Dobson Richard, Cuadrado Antonio, Hye Abdul, Ashton Nicholas J., Morgan Angharad R., Bos Isabelle, Vos Stephanie J.B., ten Kate Mara, Scheltens Philip, Vandenberghe Rik, Gabel Silvy, Meersmans Karen, Engelborghs Sebastiaan, De Roeck Ellen E., Sleegers Kristel, Frisoni Giovanni B., Blin Olivier, Richardson Jill C., Bordet Régis, Molinuevo José L., Rami Lorena, Wallin Anders, Kettunen Petronella, Tsolaki Magda, Verhey Frans, Lleó Alberto, Alcolea Daniel, Popp Julius, Peyratout Gwendoline, Martinez-Lage Pablo, Tainta Mikel, Johannsen Peter, Teunissen Charlotte E., Freund-Levi Yvonne, Frölich Lutz, Legido-Quigley Cristina, Barkhof Frederik, Blennow Kaj, Rasmussen Katrine Laura, Nordestgaard Børge Grønne, Frikke-Schmidt Ruth, Nielsen Sune Fallgaard, Soininen Hilkka, Vellas Bruno, Kloszewska Iwona, Mecocci Patrizia, Zetterberg Henrik, Morgan B. Paul, Streffer Johannes, Visser Pieter Jelle, Bertram Lars, Nevado-Holgado Alejo J., Lovestone Simon
ISSN
1387-2877
1875-8908
ISSN-L
1387-2877
Publication state
Published
Issued date
29/09/2020
Peer-reviewed
Oui
Volume
77
Number
3
Pages
1353-1368
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
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.
Keywords
Clinical Psychology, Geriatrics and Gerontology, Psychiatry and Mental health, General Medicine
Pubmed
Web of science
Open Access
Yes
Create date
03/09/2020 9:00
Last modification date
20/01/2021 7:26
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