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CDH6 and HAGH prote...
CDH6 and HAGH protein levels in plasma associate with Alzheimer’s disease in APOE ε4 carriers
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- Ahmad, Shahzad (author)
- Erasmus University Medical Center
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- Milan, Marta del Campo (author)
- Vrije Universiteit Amsterdam
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- Hansson, Oskar (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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- Demirkan, Ayse (author)
- Erasmus University Medical Center
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- Agustin, Ruiz (author)
- CIBER Enfermedades Neurodegenerativas (CIBERNED),International University of Catalonia
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Sáez, Maria E. (author)
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- Giagtzoglou, Nikolaos (author)
- Biogen, Inc.
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- Cabrera-Socorro, Alfredo (author)
- Janssen Pharmaceutica
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- Bakker, Margot H.M. (author)
- AbbVie Inc.
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- Ramirez, Alfredo (author)
- German Center for Neurodegenerative Diseases (DZNE), Bonn,University of Cologne,University of Bonn
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- Hankemeier, Thomas (author)
- Leiden University
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- Stomrud, Erik (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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- Mattsson-Carlgren, Niklas (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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- Scheltens, Philip (author)
- Vrije Universiteit Amsterdam
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- van der Flier, Wiesje M. (author)
- Vrije Universiteit Amsterdam
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- Ikram, M. Arfan (author)
- Karolinska Institutet
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- Malarstig, Anders (author)
- Karolinska Institutet
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- Teunissen, Charlotte E. (author)
- Vrije Universiteit Amsterdam
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- Amin, Najaf (author)
- Erasmus University Medical Center
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- van Duijn, Cornelia M. (author)
- Erasmus University Medical Center,University of Oxford
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(creator_code:org_t)
- 2020-05-19
- 2020
- English.
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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https://www.nature.c...
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Abstract
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- Many Alzheimer’s disease (AD) genes including Apolipoprotein E (APOE) are found to be expressed in blood-derived macrophages and thus may alter blood protein levels. We measured 91 neuro-proteins in plasma from 316 participants of the Rotterdam Study (incident AD = 161) using Proximity Extension Ligation assay. We studied the association of plasma proteins with AD in the overall sample and stratified by APOE. Findings from the Rotterdam study were replicated in 186 AD patients of the BioFINDER study. We further evaluated the correlation of these protein biomarkers with total tau (t-tau), phosphorylated tau (p-tau) and amyloid-beta (Aβ) 42 levels in cerebrospinal fluid (CSF) in the Amsterdam Dementia Cohort (N = 441). Finally, we conducted a genome-wide association study (GWAS) to identify the genetic variants determining the blood levels of AD-associated proteins. Plasma levels of the proteins, CDH6 (β = 0.638, P = 3.33 × 10−4) and HAGH (β = 0.481, P = 7.20 × 10−4), were significantly elevated in APOE ε4 carrier AD patients. The findings in the Rotterdam Study were replicated in the BioFINDER study for both CDH6 (β = 1.365, P = 3.97 × 10−3) and HAGH proteins (β = 0.506, P = 9.31 × 10−7) when comparing cases and controls in APOE ε4 carriers. In the CSF, CDH6 levels were positively correlated with t-tau and p-tau in the total sample as well as in APOE ε4 stratum (P < 1 × 10−3). The HAGH protein was not detected in CSF. GWAS of plasma CDH6 protein levels showed significant association with a cis-regulatory locus (rs111283466, P = 1.92 × 10−9). CDH6 protein is implicated in cell adhesion and synaptogenesis while HAGH protein is related to the oxidative stress pathway. Our findings suggest that these pathways may be altered during presymptomatic AD and that CDH6 and HAGH may be new blood-based biomarkers.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
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- ref (subject category)
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- By the author/editor
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Ahmad, Shahzad
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Milan, Marta del ...
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Hansson, Oskar
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Demirkan, Ayse
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Agustin, Ruiz
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Sáez, Maria E.
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show more...
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Giagtzoglou, Nik ...
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Cabrera-Socorro, ...
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Bakker, Margot H ...
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Ramirez, Alfredo
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Hankemeier, Thom ...
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Stomrud, Erik
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Mattsson-Carlgre ...
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Scheltens, Phili ...
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van der Flier, W ...
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Ikram, M. Arfan
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Malarstig, Ander ...
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Teunissen, Charl ...
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Amin, Najaf
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van Duijn, Corne ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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Scientific Repor ...
- By the university
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Lund University
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Karolinska Institutet