title: CRP gene variation affects early development of Alzheimer's disease-related plaques.
abstract: BACKGROUND
  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.
authors.affiliation: School of Medicine, University of Tampere and Centre for Laboratory Medicine, Tampere University Hospital, Tampere, Finland. Eloise.kok@uta.fi
authors.forename: Eloise Helena
authors.initials: EH
authors.lastname: Kok
authors.forename: Mervi
authors.initials: M
authors.lastname: Alanne-Kinnunen
authors.forename: Karita
authors.initials: K
authors.lastname: Isotalo
authors.forename: Teemu
authors.initials: T
authors.lastname: Luoto
authors.forename: Satu
authors.initials: S
authors.lastname: Haikonen
authors.forename: Sirkka
authors.initials: S
authors.lastname: Goebeler
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.forename: Mikko A
authors.initials: MA
authors.lastname: Hurme
authors.forename: Hannu
authors.initials: H
authors.lastname: Haapasalo
authors.forename: Pekka J
authors.initials: PJ
authors.lastname: Karhunen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D053327:Apolipoprotein E4 / Q000235:genetics; D001344:Autopsy; D002097:C-Reactive Protein / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4; D002097:C-Reactive Protein