Top

Published in:

18-10-2023 | Brief Report

KIBRA single nucleotide polymorphism is associated with hippocampal subfield volumes and cognition across development

Authors: Roya Homayouni, Ana. M. Daugherty, Qijing Yu, Naftali Raz, Noa Ofen

Published in: Brain Structure and Function | Issue 1/2024

Abstract

The hippocampus (Hc) consists of cytoarchitectonically and functionally distinct subfields: dentate gyrus (DG), cornu ammonis (CA1-3), and subiculum. In adults, a single nucleotide polymorphism (rs17070145, C→ T) in KIBRA, a gene encoding the eponymous (KIdney-BRAin) protein, is associated with variability in Hc subfield volumes and episodic memory. T-allele carriers have larger DG and CA volumes and better episodic memory compared to C-homozygotes. Little is known, however, about KIBRA’s role in the development of the brain and cognition. In a sample of children, adolescents, and young adults (N = 176, ages 5– 25 years), we replicated the adult association between KIBRA T-allele and larger DG and CA volumes but observed no relationship between KIBRA rs17070145 polymorphism and episodic memory. We noted, however, that a general cognitive performance index (IQ) differed across the allelic groups, with the lowest scores among T-homozygotes and the highest among C-homozygotes. Thus, in this developmental sample, KIBRA appears to have opposing effects on regional brain volume and cognition. These influences of KIBRA SNP may stem from associations between developmental reduction in brain volume and gains in cognitive performance—a hypothesis to be tested in longitudinal studies.

Available only for authorised users

Ahmetov II, Valeeva EV, Yerdenova MB, Datkhabayeva GK, Bouzid A, Bhamidimarri PM, Rees T (2023) KIBRA Gene variant is associated with ability in chess and science. Genes 14(1). https://doi.org/10.3390/genes14010204

Almeida OP, Schwab SG, Lautenschlager NT, Morar B, Greenop KR, Flicker L, Wildenauer D (2008) KIBRA genetic polymorphism influences episodic memory in later life, but does not increase the risk of mild cognitive impairment. J Cell Mol Med 12(5A):1672–1676. https://doi.org/10.1111/j.1582-4934.2008.00229.xCrossRefPubMedPubMedCentral

Bates TC, Price JF, Harris SE, Marioni RE, Fowkes FGR, Stewart MC, Deary IJ (2009) Association of KIBRA and memory. Neurosci Lett 458(3):140–143. https://doi.org/10.1016/j.neulet.2009.04.050

Bender AR, Keresztes A, Bodammer NC, Shing YL, Werkle-Bergner M, Daugherty AM, Raz N (2018) Optimization and validation of automated hippocampal subfield segmentation across the lifespan. Hum Brain Map 39(2):916–931. https://doi.org/10.1002/hbm.23891

Blanque A, Repetto D, Rohlmann A, Brockhaus J, Duning K, Pavenstädt H, Missler M (2015) Deletion of KIBRA, protein expressed in kidney and brain, increases filopodial-like long dendritic spines in neocortical and hippocampal neurons in vivo and in vitro. Front Neuroanatomy, 9(FEB), 1–18. https://doi.org/10.3389/fnana.2015.00013

Boraxbekk CJ, Ames D, Kochan NA, Lee T, Thalamuthu A, Wen W, Mather KA (2015) Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals. Neuropsychologia 78:10–17. https://doi.org/10.1016/j.neuropsychologia.2015.09.031

Daugherty AM, Bender AR, Raz N, Ofen N (2016) Age differences in hippocampal subfield volumes from childhood to late adulthood. Hippocampus 26(2):220–228. https://doi.org/10.1002/hipo.22517CrossRefPubMed

Daugherty AM, Flinn R, Ofen N (2017) Hippocampal CA3-dentate gyrus volume uniquely linked to improvement in associative memory from childhood to adulthood. Neuroimage. https://doi.org/10.1016/j.neuroimage.2017.03.047CrossRefPubMed

Delis DC, Kramer JH, Kaplan E, Ober BA (1994) California verbal learning test manual. San Antonio, TX: Pearson

Franks KH, Summers MJ, Vickers JC (2014) KIBRA gene polymorphism has no association with verbal or visual episodic memory performance. Frontiers in Aging Neuroscience, 6(OCT), 1–6. https://doi.org/10.3389/fnagi.2014.00270

Han SD, Bondi MW (2008) Revision of the apolipoprotein E compensatory mechanism recruitment hypothesis. Alzheimer’s Dementia 4(4):251–254. https://doi.org/10.1016/j.jalz.2008.02.006CrossRefPubMed

Han SD, Tuminello ER (2011) The apolipoprotein e antagonistic pleiotropy hypothesis: review and recommendations. Int J Alzheimer’s Dis. https://doi.org/10.4061/2011/726197CrossRef

Heitz FD, Farinelli M, Mohanna S, Kahn M, Duning K, Frey MC, Mansuy IM (2016) The memory gene KIBRA is a bidirectional regulator of synaptic and structural plasticity in the adult brain. Neurobiol Learn Memory 135:100–114. https://doi.org/10.1016/j.nlm.2016.07.028

Jacobsen LK, Picciotto MR, Heath CJ, Mencl WE (2010) Allelic variation of calsyntenin 2 (CLSTN2) modulates the impact of developmental tobacco smoke exposure on mnemonic processing in adolescents. Psychiatry: Interpersonal and Biol Process 65(8):671–679. https://doi.org/10.1016/j.biopsych.2008.10.024CrossRef

Jack CR Jr, Twomey CK, Zinsmeister AR, Sharbrough FW, Petersen RC, Cascino GD (1989) Anterior temporal lobes and hippocampal formations: normative volumetric measurements from MR images in young adults. Radiology 172(2):549–554. https://doi.org/10.1148/radiology.172.2.2748838CrossRefPubMed

Johannsen S, Duning K, Pavenstädt H, Kremerskothen J, Boeckers TM (2008) Temporal-spatial expression and novel biochemical properties of the memory-related protein KIBRA. Neuroscience 155(4):1165–1173. https://doi.org/10.1016/j.neuroscience.2008.06.054CrossRefPubMed

Jones MW, Mchugh TJ (2011) Updating hippocampal representations: CA2 joins the circuit. Trends Neurosci 34(10):526–535. https://doi.org/10.1016/j.tins.2011.07.007CrossRefPubMed

Kauppi K, Nilsson LG, Adolfsson R, Eriksson E, Nyberg L (2011) Kibra polymorphism is related to enhanced memory and elevated hippocampal processing. J Neurosci 31(40):14218–14222. https://doi.org/10.1523/JNEUROSCI.3292-11.2011CrossRefPubMedPubMedCentral

Lindenberger U, von Oertzen T, Ghisletta P, Hertzog C (2011) Cross-sectional age variance extraction: What’s change got to do with it? Psychol Aging 26(1):34–47. https://doi.org/10.1037/a0020525CrossRefPubMed

Makuch L, Volk L, Anggono V, Johnson RC, Yu Y, Duning K, Huganir RL (2011) Regulation of AMPA receptor function by the human memory-associated gene KIBRA. Neuron 71(6):1022–1029. https://doi.org/10.1016/j.neuron.2011.08.017

Milnik A, Heck A, Vogler C, Heinze HJ, de Quervain DJF, Papassotiropoulos A (2012) Association of KIBRA with episodic and working memory: a meta-analysis. Am J Med Genet Part B 159 B(8), 958–969. https://doi.org/10.1002/ajmg.b.32101

Mollon J, Knowles EEM, Mathias SR, Gur R, Peralta JM, Weiner DJ, Glahn DC (2018) Genetic influence on cognitive development between childhood and adulthood. Mol Psychiatry. https://doi.org/10.1038/s41380-018-0277-0

Muse J, Emery M, Sambataro F, Lemaitre H, Tan HY, Chen Q, Mattay VS (2014) WWC1 genotype modulates age-related decline in episodic memory function across the adult life Span. Biol Psychiatry 75(9):693–700. https://doi.org/10.1016/j.biopsych.2013.09.036

Need AC, Attix DK, McEvoy JM, Cirulli ET, Linney KN, Wagoner AP, Gumbs CE, Giegling I, Möller HJ, Francks C, Muglia P, Roses A, Gibson G, Weale ME, Rujescu D, Goldstein DB (2008) Failure to replicate effect of kibra on human memory in two large cohorts of European origin. Am J Med Genet B Neuropsychiatr Genet 147B(5):667–668 CrossRefPubMed

Palombo DJ, Amaral RSC, Olsen RK, Müller DJ, Todd RM, Anderson AK, Levine B (2013) KIBRA polymorphism is associated with individual differences in hippocampal subregions: evidence from anatomical segmentation using high-resolution MRI. J Neurosci 33(32):13088–13093. https://doi.org/10.1523/JNEUROSCI.1406-13.2013CrossRefPubMedPubMedCentral

Papassotiropoulos A, de Quervain DJF (2011) Genetics of human episodic memory: dealing with complexity. Trends Cogn Sci 15(9):381–387. https://doi.org/10.1016/j.tics.2011.07.005CrossRefPubMed

Papassotiropoulos A, Stephan DA, Huentelman MJ, Hoerndli FJ, Craig DW, Pearson JV, De Quervain DJF (2006) Common Kibra alleles are associated with human memory performance. Science 314(5798):475–478. https://doi.org/10.1126/science.1129837

Piras IS, Krate J, Schrauwen I, Corneveaux JJ, Serrano GE, Sue L, Huentelman MJ (2017) Whole transcriptome profiling of the human hippocampus suggests an involvement of the KIBRA rs17070145 polymorphism in differential activation of the MAPK signaling pathway. Hippocampus 27(7):784–793. https://doi.org/10.1002/hipo.22731

Preuschhof C, Heekeren HR, Li SC, Sander T, Lindenberger U, Bäckman L (2010) KIBRA and CLSTN2 polymorphisms exert interactive effects on human episodic memory. Neuropsychologia 48(2):402–408. https://doi.org/10.1016/j.neuropsychologia.2009.09.031CrossRefPubMed

Rasch B, Papassotiropoulos A, de Quervain DF (2010) Imaging genetics of cognitive functions: focus on episodic memory. Neuroimage 53(3):870–877. https://doi.org/10.1016/j.neuroimage.2010.01.001CrossRefPubMed

Schaper K, Kolsch H, Popp J, Wagner M, Jessen F (2008) KIBRA gene variants are associated with episodic memory in healthy elderly. Neurobiol Aging 29(7):1123–1125. https://doi.org/10.1016/j.neurobiolaging.2007.02.001CrossRefPubMed

Schuck NW, Doeller CF, Schjeide BMM, Schröder J, Frensch PA, Bertram L, Li SC (2013) Aging and KIBRA/WWC1 genotype affect spatial memory processes in a virtual navigation task. Hippocampus 23(10):919–930. https://doi.org/10.1002/hipo.22148CrossRefPubMed

Shing YL, Rodrigue KM, Kennedy KM, Fandakova Y, Bodammer, N, Werkle-Bergner M, Lindenberger U, Raz N (2011) Hippocampal subfield volumes: age vascular risk and correlation with associative memory. Front Aging Neurosci. https://doi.org/10.3389/fnagi.2011.00002CrossRefPubMedPubMedCentral

Stickel A, Kawa K, Walther K, Glisky E, Richholt R, Huentelman M, Ryan L (2018) Age-modulated associations between KIBRA, brain volume, and verbal memory among healthy older adults. Front Aging Neurosci 9(JAN):1–12. https://doi.org/10.3389/fnagi.2017.00431

Van Petten C (2004) Relationship between hippocampal volume and memory ability in healthy individuals across the lifespan: review and meta-analysis. Neuropsychologia 42(10):1394–1413. https://doi.org/10.1016/j.neuropsychologia.2004.04.006CrossRefPubMed

Witte AV, Köbe T, Kerti L, Rujescu D, Flöel A (2016) Impact of KIBRA polymorphism on memory function and the hippocampus in older adults. Neuropsychopharmacol 41(3):781–790. https://doi.org/10.1038/npp.2015.203CrossRefPubMed

Zhang H, Kranzler HR, Poling J, Gruen JR, Gelernter J (2009) Cognitive flexibility is associated with KIBRA variant and modulated by recent tobacco use. Neuropsychopharmacol 34(12):2508–2516. https://doi.org/10.1038/npp.2009.80CrossRefPubMed

Title: KIBRA single nucleotide polymorphism is associated with hippocampal subfield volumes and cognition across development
Authors: Roya Homayouni
Ana. M. Daugherty
Qijing Yu
Naftali Raz
Noa Ofen
Publication date: 18-10-2023
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 1/2024
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-023-02716-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

KIBRA single nucleotide polymorphism is associated with hippocampal subfield volumes and cognition across development

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2024

Childhood development of brain white matter myelin: a longitudinal T1w/T2w-ratio study

Twelve weeks of physical exercise breaks with coordinative exercises at the workplace increase the sulcal depth and decrease gray matter volume in brain structures related to visuomotor processes

Altered functional brain networks in coronary heart disease: independent component analysis and graph theoretical analysis

Multivariate investigation of aging in mouse models expressing the Alzheimer’s protective APOE2 allele: integrating cognitive metrics, brain imaging, and blood transcriptomics

Whole-brain gray matter maturation trajectories associated with autistic traits from adolescence to early adulthood

Different cortical connectivities in human females and males relate to differences in strength and body composition, reward and emotional systems, and memory