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.