Genetic variants in a 'cAMP element binding protein' (CREB)-dependent histone acetylation pathway influence memory performance in cognitively healthy elderly individuals

The molecular pathways underlying age-related memory changes remain unclear. There is a substantial genetic contribution to memory performance through life span. A recent study has implicated RbAp48, which mediates its effect on age-related memory decline by interacting with cyclic adenosine monophosphate responsive element binding protein (CREB) 1 binding protein and influencing this histone acetylation pathway. To validate these findings, we tested whether genetic variants in RbAp48, CREB1, and CREBBP are associated with memory performance in 3 independent data sets consisting of 2674 cognitively healthy elderly individuals. Genetic variant rs2526690 in the CREBBP gene was significantly associated with episodic memory performance (p(meta) = 3.7 x 10(-4)) in a multivariate model adjusted for age, sex, and apolipoprotein E status. Identifying genetic variants that modulate mechanisms of cognitive aging will allow identifying valid targets for therapeutic intervention. (C) 2014 Elsevier Inc. All rights reserved.