Evidence for the association of the S100beta gene with low cognitive performance and dementia in the elderly.
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.
Lambert
J-C
JC
INSERM U744, Institut Pasteur de Lille, Université de Lille 2, Lille, France. jean-charles.lambert@pasteur-lille.fr
Ferreira
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S
Gussekloo
J
J
Christiansen
L
L
Brysbaert
G
G
Slagboom
E
E
Cottel
D
D
Petit
T
T
Hauw
J-J
JJ
DeKosky
S T
ST
Richard
F
F
Berr
C
C
Lendon
C
C
Kamboh
M Ilyas
MI
Mann
D
D
Christensen
K
K
Westendorp
R
R
Amouyel
P
P
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D003072:Cognition Disorders / Q000209:etiology*; D018672:Community Health Planning; D003704:Dementia / Q000150:complications* / Q000235:genetics*; D003718:Denmark / Q000453:epidemiology; D004200:Diseases in Twins; D005260:Female; D020022:Genetic Predisposition to Disease; D015577:Geriatric Assessment; D006801:Humans; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics*; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D012737:Sex Factors; D018433:Twin Studies as Topic
D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins