The prion gene is associated with human long-term memory.

Human cognitive processes are highly variable across individuals and are influenced by both genetic and environmental factors. Although genetic variations affect short-term memory in humans, it is unknown whether genetic variability has also an impact on long-term memory. Because prion-like conformational changes may be involved in the induction of long-lasting synaptic plasticity, we examined the impact of single-nucleotide polymorphisms (SNPs) of the prion protein gene (PRNP) on long-term memory in healthy young humans. SNPs in the genomic region of PRNP were associated with better long-term memory performance in two independent populations with different educational background. Among the examined PRNP SNPs, the common Met129Val polymorphism yielded the highest effect size. Twenty-four hours after a word list-learning task, carriers of either the 129MM or the 129MV genotype recalled 17% more information than 129VV carriers, but short-term memory was unaffected. These results suggest a role for the prion protein in the formation of long-term memory in humans.

[1]  Eric R. Kandel,et al.  A Neuronal Isoform of CPEB Regulates Local Protein Synthesis and Stabilizes Synapse-Specific Long-Term Facilitation in Aplysia , 2003, Cell.

[2]  C. Farrington,et al.  Deaths from variant Creutzfeldt-Jakob disease in the UK , 2003, The Lancet.

[3]  S. Prusiner Novel proteinaceous infectious particles cause scrapie. , 1982, Science.

[4]  Christiane Ritter,et al.  Domain organization and structure–function relationship of the HET‐s prion protein of Podospora anserina , 2003, The EMBO journal.

[5]  J. Pritchard,et al.  Use of unlinked genetic markers to detect population stratification in association studies. , 1999, American journal of human genetics.

[6]  S. Gabriel,et al.  Assessing the impact of population stratification on genetic association studies , 2004, Nature Genetics.

[7]  A. Aguzzi,et al.  Mammalian Prion Biology One Century of Evolving Concepts , 2004, Cell.

[8]  E. Kandel,et al.  A Neuronal Isoform of the Aplysia CPEB Has Prion-Like Properties , 2003, Cell.

[9]  John Collinge,et al.  Homozygous prion protein genotype predisposes to sporadic Creutzfeldt–Jakob disease , 1991, Nature.

[10]  Pardis C Sabeti,et al.  Linkage disequilibrium in the human genome , 2001, Nature.

[11]  B Johansson,et al.  Substantial genetic influence on cognitive abilities in twins 80 or more years old. , 1997, Science.

[12]  M. Farrall,et al.  Sporadic--but not variant--Creutzfeldt-Jakob disease is associated with polymorphisms upstream of PRNP exon 1. , 2001, American journal of human genetics.

[13]  T. Bouchard,et al.  Familial studies of intelligence: a review. , 1981, Science.

[14]  H. True,et al.  A yeast prion provides a mechanism for genetic variation and phenotypic diversity , 2000, Nature.

[15]  F E Cohen,et al.  Prion protein gene variation among primates. , 1997, Journal of molecular biology.

[16]  A. Aguzzi,et al.  Prion research: the next frontiers , 1997, Nature.

[17]  P. Tompa,et al.  Prion proteins as memory molecules: an hypothesis. , 1998, Neuroscience.

[18]  P. Disterer,et al.  Methionine 129 Variant of Human Prion Protein Oligomerizes More Rapidly than the Valine 129 Variant , 2004, Journal of Biological Chemistry.

[19]  H. Schwarz,et al.  Genotyping of the prion protein gene at codon 129 , 1999, Acta Neuropathologica.

[20]  E. Kandel The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses , 2001, Science.

[21]  L. Squire,et al.  Retrograde amnesia and memory consolidation: a neurobiological perspective , 1995, Current Opinion in Neurobiology.

[22]  Katharina Henke,et al.  A functional genetic variation of the 5-HT2a receptor affects human memory , 2003, Nature Neuroscience.

[23]  C. Soto,et al.  Biochemical and structural studies of the prion protein polymorphism , 2001, FEBS letters.

[24]  J. Collinge,et al.  Human Prion Protein with Valine 129 Prevents Expression of Variant CJD Phenotype , 2004, Science.

[25]  S. Covey,et al.  Substantial Genetic Influence on Cognitive Abilities in Twins 80 or More Years Old , 1997 .

[26]  C. Farrington,et al.  Deaths from variant Creutzfeldt-Jakob disease , 1999, The Lancet.

[27]  M. Egan,et al.  The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function , 2003, Cell.