Is KIBRA polymorphism associated with memory performance and cognitive impairment in Alzheimer's disease?

Background: Genetic variations in a common single nucleotide polymorphism in the ninth intron of the gene have been linked to memory performance and risk of Alzheimer's disease (AD).

Objective: We examined the risk of AD related to presence of T allele (versus homozygote) and to memory performance. The role of established genetic risk factors ε4 and Met was also considered.

Methods: Participants were cognitively healthy individuals (n = 19), participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 99) and AD dementia (n = 37) from the Czech Brain Aging Study. Binary and multinomial logistic regressions compared odds of belonging to a certain diagnostic category and multivariate linear regressions assessed associations with memory.

Results: T allele was associated with increased AD dementia risk (odds ratio [OR] = 5.98, = 0.012) compared to CC genotype. In ε4 negative individuals, T allele was associated with a greater risk of both aMCI due to AD (OR = 6.68, = 0.038) and AD dementia (OR = 15.75, = 0.009). In Met positive individuals, the T allele was associated with a greater risk of AD dementia (OR = 10.98, = 0.050). In AD dementia, the association between T allele and better memory performance approached significance (β = 0.42; = 0.062). The link between possessing the T allele and better memory reached statistical significance only among Met carriers (β = 1.21, = 0.027).

Conclusions: Findings suggest that T allele may not fully protect against AD dementia but could potentially delay progression of post-diagnosis cognitive deficits.