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Association of IL1RAP-related genetic variation with cerebrospinal fluid concentration of Alzheimer-associated tau protein

Zettergren, Anna; Höglund, Kina; Kern, Silke; Thorvaldsson, Valgeir; Johan Skoog, Msc; Hansson, Oskar LU ; Andreasen, Niels; Bogdanovic, Nenad; Blennow, Kaj LU and Skoog, Ingmar, et al. (2019) In Scientific Reports 9(1).
Abstract


A possible involvement of the gene IL1RAP (interleukin-1 receptor-associated protein) in the pathogenesis of Alzheimer’s disease (AD) has been suggested in GWASs of cerebrospinal fluid (CSF) tau levels and longitudinal change in brain amyloid burden. The aim of this study was to examine previously implicated genetic markers in and near IL1RAP in relation to AD risk, CSF tau and Aβ biomarkers, as well as cognitive decline, in a case (AD)-control study and an age homogenous population-based cohort. Genotyping of IL1RAP-related single nucleotide polymorphisms (SNPs), selected based on previous GWAS results, was performed. 3446 individuals (1154 AD cases and 2292 controls) were... (More)


A possible involvement of the gene IL1RAP (interleukin-1 receptor-associated protein) in the pathogenesis of Alzheimer’s disease (AD) has been suggested in GWASs of cerebrospinal fluid (CSF) tau levels and longitudinal change in brain amyloid burden. The aim of this study was to examine previously implicated genetic markers in and near IL1RAP in relation to AD risk, CSF tau and Aβ biomarkers, as well as cognitive decline, in a case (AD)-control study and an age homogenous population-based cohort. Genotyping of IL1RAP-related single nucleotide polymorphisms (SNPs), selected based on previous GWAS results, was performed. 3446 individuals (1154 AD cases and 2292 controls) were included in the analyses of AD risk, 1400 individuals (cognitively normal = 747, AD = 653) in the CSF biomarker analyses, and 861 individuals in the analyses of cognitive decline. We found no relation between IL1RAP-related SNPs and AD risk. However, CSF total-tau and phospho-tau were associated with the SNP rs9877502 (p = 6 × 10
−3
and p = 5 × 10
−4
). Further, nominal associations (p = 0.03–0.05) were found between three other SNPs and CSF biomarker levels, or levels of cognitive performance and decline in a sub-sample from the general population. These results support previous studies suggesting an association of IL1RAP with disease intensity of AD.

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Scientific Reports
volume
9
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85061907372
ISSN
2045-2322
DOI
10.1038/s41598-018-36650-3
language
English
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yes
id
45cfa776-3e91-4c60-8dbb-65ff3f9a3095
date added to LUP
2019-03-01 09:06:02
date last changed
2019-03-27 04:39:28
@article{45cfa776-3e91-4c60-8dbb-65ff3f9a3095,
  abstract     = {<p><br>
                                                         A possible involvement of the gene IL1RAP (interleukin-1 receptor-associated protein) in the pathogenesis of Alzheimer’s disease (AD) has been suggested in GWASs of cerebrospinal fluid (CSF) tau levels and longitudinal change in brain amyloid burden. The aim of this study was to examine previously implicated genetic markers in and near IL1RAP in relation to AD risk, CSF tau and Aβ biomarkers, as well as cognitive decline, in a case (AD)-control study and an age homogenous population-based cohort. Genotyping of IL1RAP-related single nucleotide polymorphisms (SNPs), selected based on previous GWAS results, was performed. 3446 individuals (1154 AD cases and 2292 controls) were included in the analyses of AD risk, 1400 individuals (cognitively normal = 747, AD = 653) in the CSF biomarker analyses, and 861 individuals in the analyses of cognitive decline. We found no relation between IL1RAP-related SNPs and AD risk. However, CSF total-tau and phospho-tau were associated with the SNP rs9877502 (p = 6 × 10                             <br>
                            <sup>−3</sup><br>
                                                          and p = 5 × 10                             <br>
                            <sup>−4</sup><br>
                                                         ). Further, nominal associations (p = 0.03–0.05) were found between three other SNPs and CSF biomarker levels, or levels of cognitive performance and decline in a sub-sample from the general population. These results support previous studies suggesting an association of IL1RAP with disease intensity of AD.                         <br>
                        </p>},
  articleno    = {2460},
  author       = {Zettergren, Anna and Höglund, Kina and Kern, Silke and Thorvaldsson, Valgeir and Johan Skoog, Msc and Hansson, Oskar and Andreasen, Niels and Bogdanovic, Nenad and Blennow, Kaj and Skoog, Ingmar and Zetterberg, Henrik},
  issn         = {2045-2322},
  language     = {eng},
  month        = {02},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Association of IL1RAP-related genetic variation with cerebrospinal fluid concentration of Alzheimer-associated tau protein},
  url          = {http://dx.doi.org/10.1038/s41598-018-36650-3},
  volume       = {9},
  year         = {2019},
}