Associations of Gene Sequence Variation and Serum Levels of C-Reactive Protein and Interleukin-6 with Alzheimer's Disease and Dementia

Abstract

Inflammatory mechanisms have been implicated in Alzheimer's disease (AD) and dementia. We therefore sought to study DNA sequence variation and serum levels of the potent inflammatory mediators Interleukin-6 (IL6) and C-reactive protein (CRP) in relation to AD and dementia. Tagging single nucleotide polymorphisms (tagSNPs) were chosen to capture most variation in and around CRP and IL6 in 3937 elderly Swedish men and women (1,265 AD cases). A sub-set of the population (n = 723) with serum measurements of CRP and IL6 was included in 1) a nested case-control study of incident dementia cases, and 2) a case-control study of prevalent dementia cases. None of the SNPs or haplotypes was significantly associated with AD or dementia after correcting for multiple testing nor were elevated baseline levels of hsCRP or IL6 (measured on average 4.3 years before dementia onset) significantly associated with risk of future AD or dementia. However, prevalent AD cases had higher levels of IL6 (measured on average 5.5 years after dementia onset) than age- and gender-matched controls, OR 2.24 (95% CI 1.27–3.95), p-value 0.006. In summary, this data suggests that AD patients have an altered immune profile with higher circulating levels of IL6 than age- and gender-matched controls. However, neither variation in the CRP and IL6 genes nor circulating levels of their respective protein products were associated with an increased risk of developing late-life dementias.