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

Variations in the S100 beta gene may be instrumental in producing a continuum from mild cognitive decline to overt dementia. After screening 25 single nucleotide polymorphisms (SNPs) in S100 beta, 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 S100 beta 2). S100 beta 2 expression was increased in AD brain compared with controls, and the rs2300403 SNP was associated with elevated levels of S100 beta 2 mRNA in AD brains, especially in women. Therefore, this genetic variant in S100 beta increases the risk of low cognitive performance and dementia, possibly by favouring a splicing event increasing S100 beta 2 isoform expression in the brain.