Yebenes_article_EU Neurology 12/03/2010 11:44 Page 127
Environmental and Genetic Risk Factors for Alzheimer’s Disease in Spain
Table 3: Genetic Risk Factors for Alzheimer’s Disease and Dementia in Spain
Gene Protein Function Variation Type of Study Effect Reference
ApoE Mediates the binding, Allele ε4 Increased risk of AD 45
internalisation and catabolism
of lipoprotein particles
14-3-3 Zeta (tyrosine The 14-3-3 family of proteins mediates 14-3-3 Zeta rs983583 + CC Decreased risk of AD 31
3-monooxygenase/tryptophan signal transduction by binding to Tau rs2471738 2.5-fold
5-monooxygenase activation phosphoserine-containing proteins
protein, zeta isoform)
Tau (microtubule-associated Promotes microtubule assembly
protein tau) and stability and might be involved in
the establishment and maintenance
of neuronal polarity
IL-10 Inhibits the synthesis of a number IL-10 rs1800896 + CC Decreased risk of AD 32
of cytokines, including IFN-gamma, CYP19 rs1062033 6-fold
IL-2, IL-3, TNF and GM-CSF produced
by activated macrophages and by
helper T cells
CYP19 (aromatase) Catalyses the formation of aromatic
C18 estrogens from C19 androgens
14-3-3 Zeta Mutant alleles at the BCHE 14-3-3 zeta protein CC Decreased risk of AD 33
BCHE (butyrilcholinesterase) locus are responsible for rs964917 + BCHEK variant
suxamethonium sensitivity
14-3-3 Zeta 14-3-3 zeta protein rs 983583+
BCHE BCHE Ala539Thr
CD14 CD14 rs2569190 + LXRb CC Decreased risk of AD 34
LXR Beta rs1052533 6-fold
BACE 1 BACE1 exon 5 G/C + ApoE ε4 Increased risk of AD 35
ApoE
OLR1 3’UTR (+1071 A) + (+1073C) Increased level of
astrocyte activation
in AD
VLDLR 5’UTR (CGG)n allele5 Risk factor in Asian
people but protective
factor in Caucasians
ABCA1 Haplotype (R219K, CC Increased risk of AD 36
I883M, R1587K) 1.75-fold
PRNP129 PRNP129 (Met129Met) + IL1A CC Increased risk of AD 37
IL-1A (-889 allele 2) 3.0-fold
ER α (ostrogen receptor alpha) ER α (-401CC) + BCHEK variant CC Decreased risk of AD 38
BCHE
PARP-1 (poly(ADP ribose) PARP-1 haplotype (-410, -1672) CC Increased risk of AD 39
polymerase 1)
PARP-1 (poly(ADP ribose) PARP-1 haplotype (-410, -1672)+
polymerase 1) IL1A (-889 allele2)
IL-1
Glycogen synthase kinase-3 α Glycogen synthase kinase-3 α CC Increased risk of 40
STH (saitohin) (-50 TT promoter) + STH(Q7R) late-onset AD
BBH (dopamine beta-hydrolase) BBH (-1021C/T promoter)+ CC Increased risk of 41
IL-1(-889 allele 2) + IL-6 late-onset AD
(-174 allele G)
IL-1
IL-6
CETP (cholesteryl ester CETP -629 C/A+ ApoE ε4 CC Decreased risk of AD 42
transfer protein) approximately 3-fold
ApoE in ApoE ε4 carriers
IL-6 IL-6 (-174 C/C) CC Decreased risk of AD 43
IL-6 IL-6 (-174 C/C) + ICAM1 (K469K) Decreased risk of AD
ICAM1 (intercellular
adhesion molecule1)
IL-6 IL-6 (-174 C/C) + IL-10 (-1082 A/A) CC Decreased risk of AD 44
IL-10 6-fold
AD = Alzheimer’s disease; IFN = interferon; TNF = tumour necrosis factor; GM-CSF = granulocyte macrophage colony-stimulating factor; CC = case control study; R = review; IL = interleukin.
EUROPEAN NEUROLOGICAL REVIEW 127
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