Session Title: Inflammation
Presentation Date: Friday, March 14 – Saturday, March 15, 2009
ASSOCIATION OF GENETIC VARIATION OF CRP WITH ALZHEIMER'S DISEASE-RELATED SENILE PLAQUES AND NEUROFIBRILLARY TANGLES
E. Kok1, M. Alanne2, S. Haikonen1, T. Luoto1, H. Huhtala3, L. Viiri1, K. Kristiansson2, M. Hurme4, H. Haapasalo5, M. Perola2, P. Karhunen1
1University of Tampere, Forensic Medicine, Tampere, Finland, 2National Public Health Institute, Molecular Medicine, Helsinki, Finland, 3University of Tampere, School of Public Health, Tampere, Finland, 4University of Tampere, Immunology, Tampere, Finland, 5Tampere University Hospital, Pathology, Centre for Laboratory Medicine, Tampere, Finland
APOE epsilon4 is associated with AD (Kivipelto et al 2002), although the exact mechanism is unknown. Inflammation plays a part (Block et al 2007), although whether it is causative or a result is debated. CRP, an inflammatory indicator (Uchikado et al 2004), recently shown to be involved in increased mortality of patients (Hurme et al 2007), is expressed in pyramidal neurons of AD patients, and upregulated in AD affected brain areas (Yasojima et al 2000).
We investigated 603 men and women (aged 0-97 years) who died out-of-hospital in Tampere (Finland) during 2002-2004. SP frequencies (frontal cortex) and NFT (hippocampus) were scored using a modified CERAD protocol. CRP genotyping used Sequenom (6 SNPs).
31.0% of cases had >=1 SP, with a strong correlation with age (rS = 0.46, p < 0.001). 42.1% had NFT, which also had a strong relationship with age (rS = 0.52, p < 0.001). No correlations between >=1 SP or NFT were found between the SNPs studied, however differentiating SP by plaque type (diffuse, primitive, classic, burnt out) revealed a statistically significant difference between incidence and polymorphisms of rs2794521 (p = 0.042) and rs1205 (p = 0.005). Cross tabulations between incidence of neuritic versus non-neuritic plaques also exposed statistically significant differences between polymorphisms of rs2794521 (p = 0.049), rs3091244 (p = 0.045) and rs3093075 (p = 0.023).
CRP gene variation correlates with the presence of certain types of SP, associated with AD, supporting the theory inflammation plays a role in pathogenesis of the disease.