title: Genetic variants in a 'cAMP element binding protein' (CREB)-dependent histone acetylation pathway influence memory performance in cognitively healthy elderly individuals.
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.
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Barral
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
authors.forename: Christiane
authors.initials: C
authors.lastname: Reitz
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Small
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA. Electronic address: rpm2@cumc.columbia.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
mesh_terms: D000107:Acetylation; D000375:Aging / Q000235:genetics* / Q000523:psychology*; D050882:CREB-Binding Protein / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D056726:Genetic Association Studies; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008568:Memory / Q000502:physiology*; D061212:Memory, Episodic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D056505:Retinoblastoma-Binding Protein 4 / Q000235:genetics*
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D006657:Histones; C082637:RBBP4 protein, human; D056505:Retinoblastoma-Binding Protein 4; D050882:CREB-Binding Protein; C494363:CREBBP protein, human
keywords: Episodic memory performance; Histone metabolism; Meta-analysis