Evidence for the association of the S100β gene with low cognitive performance and dementia in the elderly

J-C Lambert, S Ferreira, J Gussekloo, L Christiansen, G Brysbaert, E Slagboom, D Cottel, T Petit, J-J Hauw, T DeKosky, F Richard, C Berr, Corinne Lendon, M Ilyas Kamboh, D Mann, K Christensen, R Westendorp, P Amouyel

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    Variations in the S100beta gene may be instrumental in producing a continuum from mild cognitive decline to overt dementia. After screening 25 single nucleotide polymorphisms (SNPs) in S100beta, we observed association of the rs2300403 intron 2 SNP with poorer cognitive function in three independent populations. Moreover, we detected a significant association of this SNP with increased risk of developing dementia or Alzheimer's disease (AD) in six independent populations, especially in women and in the oldest. Furthermore, we characterised a new primate-specific exon within intron 2 (the corresponding mRNA isoform was called S100beta2). S100beta2 expression was increased in AD brain compared with controls, and the rs2300403 SNP was associated with elevated levels of S100beta2 mRNA in AD brains, especially in women. Therefore, this genetic variant in S100beta increases the risk of low cognitive performance and dementia, possibly by favouring a splicing event increasing S100beta2 isoform expression in the brain.
    Original languageEnglish
    Pages (from-to)870-880
    Number of pages11
    JournalMolecular Psychiatry
    Volume12
    DOIs
    Publication statusPublished - 6 Mar 2007

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