van Oijen M et al. (2006) Polymorphisms and haplotypes in the C-reactive protein gene and risk of dementia. Neurobiol Aging [doi:10.1016/j.neurobiolaging.2006.06.015]

Inflammation is postulated to be involved in the etiology of dementia, and the inflammatory mediator C-reactive protein (CRP) is present in the brains of patients with dementia; however, studies examining the relationship between serum levels of CRP and dementia have produced inconsistent results. van Oijen et al. suggest that lifelong CRP exposure (determined in part by genetic factors) might be associated with the risk of dementia.

In a prospective, population-based study, the researchers examined the association between CRP genotype and the risk of developing dementia. All study participants resided in a single district in The Netherlands, and were aged ≥55 years. The CRP genotype of each participant (n = 5,972) was determined, and late-life serum CRP measurements taken. Presence or absence of an APOEε4 allele was also established, as carriers have been shown to have lower serum levels of CRP.

Over a mean follow-up of 9.2 years, 607 individuals were diagnosed with incident dementia. In analyses adjusted for age and sex, the T allele of the CRP 2042 C>T polymorphism was associated with a lower late-life serum CRP level and a lower risk of dementia that was independent of late-life serum CRP level. The lower risk of dementia associated with the T allele of the CRP 2042 C>T polymorphism was most pronounced in APOEε4 carriers. Although further studies are required, the authors conclude that lifelong cumulative exposure to CRP is associated with risk of dementia.