Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Research Article
  • Published:

M129V variation in the prion protein may influence cognitive performance

Molecular Psychiatry volume 8, pages 937–941 (2003)Cite this article

Abstract

Correlations between general intelligence (g) and brain volume are about 0.40, and the correlation between g and white matter volume has been reported to be largely due to genetic factors. Establishing that the correlation between brain volumes and cognitive abilities is mediated by shared genetic factors is only the first step in unveiling the relation between them. We have recently shown that methionine at codon 129 in the prion protein is associated with white matter reduction in a group of healthy volunteers and schizophrenic patients. The present study examines the influence of the same genetic variation on psychometric cognitive performance measurements in 335 community-based healthy volunteers. The polymorphism was associated with Full Scale IQ (genotype: F=4.38, df=2/317, P=0.013; allele: F=8.04, df=1/658, P=0.005), as measured by HAWIE-R (German version of the Wechsler Adult Intelligence Scale, Revised). Genotype accounted for 2.7% of the total variability in Full Scale IQ (partial η2=0.027). An exploratory analysis revealed association with several HAWIE-R subscales; the association with the Digit Symbol subtest remained significant after correction for multiple testing. In summary, we deliver evidence for an association of a common genetic variation in the prion protein gene with cognitive performance. However, independent replications are needed before firm conclusions can be drawn.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Plomin R, Petrill S . Genetics and intelligence: what's new? Intelligence 1997; 24: 53–77.

    Article  Google Scholar 

  2. Bouchard TJ . Genetic and environmental influences on adult intelligence and special mental abilities. Hum Biol 1998; 70: 257–279.

    PubMed  Google Scholar 

  3. Baare WF, Hulshoff Pol HE, Boomsma DI, Posthuma D, de Geus EJ, Schnack HG et al. Quantitative genetic modeling of variation in human brain morphology. Cereb Cortex 2001; 11: 816–824.

    Article  CAS  Google Scholar 

  4. Vernon PA, Wickett JC, Banzana PG, Stelmack RM . The neuropsychology and psychophysiology of human intelligence. In: Sternberg RJ (ed). Handbook of Intelligence. Cambridge University Press: Cambridge, 2000, pp 245–264.

    Chapter  Google Scholar 

  5. Plomin R, Kosslyn SM . Genes, brain and cognition. Nat Neurosci 2001; 4: 1153–1154.

    Article  CAS  Google Scholar 

  6. Posthuma D, De Geus EJC, Baaré WFC, Pol HEH, Kahn RS, Boomsma DI . Nat Neurosci 2002; 5: 83–84.

    Article  CAS  Google Scholar 

  7. Rujescu D, Meisenzahl EM, Giegling I, Kirner A, Leinsinger G, Hegerl U et al. Methionine homozygosity at codon 129 in the prion protein is associated with white matter reduction and enlargement of CSF compartments in healthy volunteers and schizophrenic patients. Neuroimage. 2002; 15: 200–206.

    Article  CAS  Google Scholar 

  8. Lemaire-Vieille C, Schulze T, Podevin-Dimster V, Follet J, Bailly Y, Blanquet-Grossard F et al. Epithelial and endothelial expression of the green fluorescent protein reporter gene under the control of bovine prion protein (PrP) gene regulatory sequences in transgenic mice. Proc Natl Acad Sci USA 2000; 97: 5422–5427.

    Article  CAS  Google Scholar 

  9. Herms J, Tings T, Gall S, Madlung A, Giese A, Siebert H et al. Evidence of presynaptic location and function of the prion protein. J Neurosci 1999; 19: 8866–8875.

    Article  CAS  Google Scholar 

  10. Collinge J, Whittington MA, Sidle KCL, Smith CJ, Palmer MS, Clarke AR et al. Prion protein is necessary for normal synaptic function. Nature 1994; 370: 295–297.

    Article  CAS  Google Scholar 

  11. Brown DR . Prion protein expression aids cellular uptake and veratridine-induced release of copper. J Neurosci Res 1999; 58: 717–725.

    Article  CAS  Google Scholar 

  12. Brown DR, Besinger A . Prion protein expression and superoxide dismutase activity. Biochem J 1998; 334: 423–429.

    Article  CAS  Google Scholar 

  13. Wong BS, Pan T, Liu T, Li R, Gambetti P, Sy MS . Differential contribution of superoxide dismutase activity by prion protein in vivo. Biochem Biophys Res Commun 2000; 273: 136–139.

    Article  CAS  Google Scholar 

  14. Mouillet-Richard S, Laurendeau I, Vidaud M, Kellermann O, Laplanche JL . Prion protein and neuronal differentiation: quantitative analysis of prnp gene expression in a murine inducible neuroectodermal progenitor. Microbes Infect 1999; 1: 969–976.

    Article  CAS  Google Scholar 

  15. Satoh J, Kuroda Y, Katamine S . Gene expression profile in prion protein-deficient fibroblasts in culture. Am J Pathol 2000; 157: 59–68.

    Article  CAS  Google Scholar 

  16. Rowe DC, Jacobson KC, Van den Oord EJ . Genetic and environmental influences on vocabulary IQ: parental education level as moderator. Child Dev 1999; 70: 1151–1162.

    Article  CAS  Google Scholar 

  17. Wong BS, Clive C, Haswell SJ, Williamson RA, Burton DR, Gambetti P et al. Copper has differential effect on prion protein with polymorphism of position 129. Biochem Biophys Res Commun 2000; 269: 726–731.

    Article  CAS  Google Scholar 

  18. Fydrich Z, Renneberg B, Schmitz B, Wittchen HU . Strukturiertes Klinisches Interview für DSM-IV, Achse II: Persönlichkeitsstörungen. Hogrefe: Goettingen, 1997.

    Google Scholar 

  19. Wittchen HU, Zaudig M, Fydrich T . Strukturiertes Klinisches Interview für DSM-IV, Achse I und II. Hogrefe: Goettingen, 1997.

    Google Scholar 

  20. Rice JP, Reich T, Bucholz KK, Neuman RJ, Fishman R, Rochberg N et al. Comparison of direct interview and family history diagnoses of alcohol dependence. Alcohol Clin Exp Res 1995; 19: 1018–1023.

    Article  CAS  Google Scholar 

  21. Tewes U . HAWIE-R Hamburg-Wechsler Intelligenztest für Erwachsene. Revision 1991. Hogrefe: Goettingen, 1991.

    Google Scholar 

Download references

Acknowledgements

We thank Stephany Fulda for helpful discussions. Parts of this work are taken from the MD thesis of Tanja Schulz.

Author information

Authors and Affiliations

  1. Division of Molecular Neurobiology, Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany

    D Rujescu, A M Hartmann, C Gonnermann, H-J Möller & I Giegling

Authors
  1. D Rujescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A M Hartmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Gonnermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H-J Möller
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I Giegling
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D Rujescu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rujescu, D., Hartmann, A., Gonnermann, C. et al. M129V variation in the prion protein may influence cognitive performance. Mol Psychiatry 8, 937–941 (2003). https://doi.org/10.1038/sj.mp.4001327

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4001327

Keywords

This article is cited by

Search

Advanced search

Quick links