CRP gene variation affects early development of Alzheimer's disease-related plaques
Kok, Eloise H; Alanne-Kinnunen, Mervi; Isotalo, Karita; Luoto, Teemu; Haikonen, Satu; Goebeler, Sirkka; Perola, Markus; Hurme, Mikko; Haapasalo, Hannu; Karhunen, Pekka J (2011)
Kok, Eloise H
Alanne-Kinnunen, Mervi
Isotalo, Karita
Luoto, Teemu
Haikonen, Satu
Goebeler, Sirkka
Perola, Markus
Hurme, Mikko
Haapasalo, Hannu
Karhunen, Pekka J
2011
Journal of Neuroinflammation 8
96
Biolääketieteellisen teknologian yksikkö - Institute of Biomedical Technology
Lääketieteen yksikkö - School of Medicine
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Julkaisun pysyvä osoite on
https://urn.fi/urn:nbn:uta-3-661
https://urn.fi/urn:nbn:uta-3-661
Kuvaus
BioMed Central Open access
Tiivistelmä
Introduction
We used the Tampere Autopsy Study (TASTY) series (n = 603, age 0-97 yrs), representing an unselected population outside institutions, to investigate the pathogenic involvement of inflammation in Alzheimer's disease-related lesions.
Methods
We studied senile plaque (SP), neurofibrillary tangles (NFT) and SP phenotype associations with 6 reported haplotype tagging single nucleotide polymorphisms (SNPs) in the CRP gene. CRP and Aβ immunohistochemistry was assessed using brain tissue microarrays.
Results
In multivariate analyses (age- and APOE-adjusted), non-neuritic SP were associated with the high-CRP TA-genotype (3.0% prevalence) of rs3091244 and CA-genotype (10.8%) of rs3093075 compared to common genotypes. Conversely, the low-CRP C allele (39.3%) of rs2794521 reduced the risk of harbouring early non-neuritic SP, compared to the TT genotype. CRP haplotype TAGCC (high) associated with non-neuritic SP, whereas haplotype CCGCC offered protection. TT genotypes (high) of rs3091244 and rs1130864 were associated with CRP staining. There were no associations between SNPs or haplotypes and NFT. CRP staining of the hippocampal CA1/2 region correlated with Aβ staining.
Conclusions
CRP gene variation affects early SP development in prodromal Alzheimer's disease, independent of APOE genotype.
We used the Tampere Autopsy Study (TASTY) series (n = 603, age 0-97 yrs), representing an unselected population outside institutions, to investigate the pathogenic involvement of inflammation in Alzheimer's disease-related lesions.
Methods
We studied senile plaque (SP), neurofibrillary tangles (NFT) and SP phenotype associations with 6 reported haplotype tagging single nucleotide polymorphisms (SNPs) in the CRP gene. CRP and Aβ immunohistochemistry was assessed using brain tissue microarrays.
Results
In multivariate analyses (age- and APOE-adjusted), non-neuritic SP were associated with the high-CRP TA-genotype (3.0% prevalence) of rs3091244 and CA-genotype (10.8%) of rs3093075 compared to common genotypes. Conversely, the low-CRP C allele (39.3%) of rs2794521 reduced the risk of harbouring early non-neuritic SP, compared to the TT genotype. CRP haplotype TAGCC (high) associated with non-neuritic SP, whereas haplotype CCGCC offered protection. TT genotypes (high) of rs3091244 and rs1130864 were associated with CRP staining. There were no associations between SNPs or haplotypes and NFT. CRP staining of the hippocampal CA1/2 region correlated with Aβ staining.
Conclusions
CRP gene variation affects early SP development in prodromal Alzheimer's disease, independent of APOE genotype.
Kokoelmat
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