title: WWC1 genotype modulates age-related decline in episodic memory function across the adult life span.
abstract: BACKGROUND
  Episodic memory (EM) declines with age and the rate of decline is variable across individuals. A single nucleotide polymorphism (rs17070145) in the WWC1 gene that encodes the KIBRA protein critical for long-term potentiation and memory consolidation has previously been associated with EM performance, as well as differences in hippocampal engagement during EM tasks using functional magnetic resonance imaging (fMRI). In the current study, we explore the effect of this polymorphism on EM-related activity and cognitive performance across the adult life span using fMRI.
  
  
  METHODS
  Two hundred thirty-two healthy, Caucasian subjects (18-89 years) completed a battery of cognitive tests, as well as an EM task during an fMRI scan.
  
  
  RESULTS
  WWC1 T carriers had significantly better delayed recall performance than CC individuals (p = .006). The relationship between increasing age and recall scores (immediate and delayed) was also significantly different between WWC1 genotype groups (p = .01). In addition to the age-related decline in hippocampal formation (HF) activation (p < .05; false discovery ratesmall volume correction-HF-region of interest), we observed an age by WWC1 genotype interaction on HF activation during encoding and retrieval. The CC group showed a significant negative association between HF activity and increasing age, while no such association was observed in the T carrier group (left HF p = .04; r-z correlation difference during encoding and retrieval; right HF p = .0008; r-z correlation difference during retrieval).
  
  
  CONCLUSIONS
  Our results show a dynamic relationship between rs17070145 polymorphism and increasing age on neuronal activity in the hippocampal region.
authors.affiliation: Clinical Brain Disorders Branch (JM, ME, FS, HL, H-YT, QC, BSK, SD, JHC, DRW, VSM), Genes Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda; Lieber Institute for Brain Development (JM, H-YT, QC, DRW, VSM), Johns Hopkins University Medical Campus, Baltimore.
authors.forename: John
authors.initials: J
authors.lastname: Muse
authors.affiliation: Clinical Brain Disorders Branch (JM, ME, FS, HL, H-YT, QC, BSK, SD, JHC, DRW, VSM), Genes Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda.
authors.forename: Matthew
authors.initials: M
authors.lastname: Emery
authors.affiliation: Clinical Brain Disorders Branch (JM, ME, FS, HL, H-YT, QC, BSK, SD, JHC, DRW, VSM), Genes Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda.
authors.forename: Fabio
authors.initials: F
authors.lastname: Sambataro
authors.affiliation: Clinical Brain Disorders Branch (JM, ME, FS, HL, H-YT, QC, BSK, SD, JHC, DRW, VSM), Genes Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda.
authors.forename: Herve
authors.initials: H
authors.lastname: Lemaitre
authors.affiliation: Clinical Brain Disorders Branch (JM, ME, FS, HL, H-YT, QC, BSK, SD, JHC, DRW, VSM), Genes Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda; Lieber Institute for Brain Development (JM, H-YT, QC, DRW, VSM), Johns Hopkins University Medical Campus, Baltimore.
authors.forename: Hao-Yang
authors.initials: HY
authors.lastname: Tan
authors.affiliation: Clinical Brain Disorders Branch (JM, ME, FS, HL, H-YT, QC, BSK, SD, JHC, DRW, VSM), Genes Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda; Lieber Institute for Brain Development (JM, H-YT, QC, DRW, VSM), Johns Hopkins University Medical Campus, Baltimore.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Clinical Brain Disorders Branch (JM, ME, FS, HL, H-YT, QC, BSK, SD, JHC, DRW, VSM), Genes Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda.
authors.forename: Bhaskar S
authors.initials: BS
authors.lastname: Kolachana
authors.affiliation: Clinical Brain Disorders Branch (JM, ME, FS, HL, H-YT, QC, BSK, SD, JHC, DRW, VSM), Genes Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda.
authors.forename: Saumitra
authors.initials: S
authors.lastname: Das
authors.affiliation: Clinical Brain Disorders Branch (JM, ME, FS, HL, H-YT, QC, BSK, SD, JHC, DRW, VSM), Genes Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Callicott
authors.affiliation: Clinical Brain Disorders Branch (JM, ME, FS, HL, H-YT, QC, BSK, SD, JHC, DRW, VSM), Genes Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda; Lieber Institute for Brain Development (JM, H-YT, QC, DRW, VSM), Johns Hopkins University Medical Campus, Baltimore; Departments of Neurology (DRW); Psychiatry, Neuroscience and the Institute of Genetic Medicine (DRW), Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
authors.affiliation: Clinical Brain Disorders Branch (JM, ME, FS, HL, H-YT, QC, BSK, SD, JHC, DRW, VSM), Genes Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda; Lieber Institute for Brain Development (JM, H-YT, QC, DRW, VSM), Johns Hopkins University Medical Campus, Baltimore. Electronic address: anand.mattay@libd.org.
authors.forename: Venkata S
authors.initials: VS
authors.lastname: Mattay
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000502:physiology*; D001921:Brain / Q000502:physiology; D001931:Brain Mapping; D005838:Genotype; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007858:Learning / Q000502:physiology; D008279:Magnetic Resonance Imaging; D061212:Memory, Episodic; D011939:Mental Recall; D008875:Middle Aged; D009483:Neuropsychological Tests; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C513637:WWC1 protein, human
keywords: Aging; KIBRA; WWC1; episodic memory (EM); hippocampus; long-term potentiation (LTP); single nucleotide polymorphism (SNP)