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

Variations in the S100β gene may be instrumental in producing a continuum from mild cognitive decline to overt dementia. After screening 25 single nucleotide polymorphisms (SNPs) in S100β, 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 S100β2). S100β2 expression was increased in AD brain compared with controls, and the rs2300403 SNP was associated with elevated levels of S100β2 mRNA in AD brains, especially in women. Therefore, this genetic variant in S100β increases the risk of low cognitive performance and dementia, possibly by favouring a splicing event increasing S100β2 isoform expression in the brain. © 2007 Nature Publishing Group All rights reserved.