Genetic variants in a 'cAMP element binding protein' (CREB)-dependent histone acetylation pathway influence memory performance in cognitively healthy elderly individuals.
Title | Genetic variants in a 'cAMP element binding protein' (CREB)-dependent histone acetylation pathway influence memory performance in cognitively healthy elderly individuals. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Barral, S, Reitz, C, Small, SA, Mayeux, R |
Journal | Neurobiol Aging |
Volume | 35 |
Issue | 12 |
Pagination | 2881.e7-2881.e10 |
Date Published | 2014 Dec |
ISSN | 1558-1497 |
Keywords | Acetylation, Aging, Cognition, Cohort Studies, CREB-Binding Protein, Cyclic AMP Response Element-Binding Protein, Genetic Association Studies, Histones, Humans, Memory, Memory, Episodic, Polymorphism, Single Nucleotide, Retinoblastoma-Binding Protein 4 |
Abstract | 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 (pmeta = 3.7 × 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. |
DOI | 10.1016/j.neurobiolaging.2014.06.024 |
Alternate Journal | Neurobiol. Aging |
PubMed ID | 25150575 |
PubMed Central ID | PMC4253058 |
Grant List | U01-AG032984 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States U24-AG026395 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States P01 AG007232 / AG / NIA NIH HHS / United States U24-AG21886 / AG / NIA NIH HHS / United States U24 AG026395 / AG / NIA NIH HHS / United States R01 AG041797 / AG / NIA NIH HHS / United States R01-AG037212 / AG / NIA NIH HHS / United States R01-AG041797 / AG / NIA NIH HHS / United States R01 AG037212 / AG / NIA NIH HHS / United States P01-AG007232 / AG / NIA NIH HHS / United States U01-AG016976 / AG / NIA NIH HHS / United States |