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

Artikel i vetenskaplig tidskrift
Författare Anna Zettergren
Kina Höglund
Silke Kern
Valgeir Thorvaldsson
Johan Skoog
O. Hansson
N. Andreasen
N. Bogdanovic
Kaj Blennow
Ingmar Skoog
Henrik Zetterberg
Publicerad i Scientific Reports
Volym 9
ISSN 2045-2322
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Centrum för åldrande och hälsa (AgeCap)
Språk en
Länkar dx.doi.org/10.1038/s41598-018-36650...
Ämnesord mini-mental-state, interleukin-1-beta polymorphisms, microglial, activation, disease, pathology, dementia, markers, onset, risk, gwas, Science & Technology - Other Topics, khann g, 1984, neurology, v34, p939, lstein mf, 1975, journal of psychiatric research, v12, p189
Ämneskategorier Psykiatri

Sammanfattning

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 A beta 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 x 10(-3) and p = 5 x 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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