Association of the RAGE G82S polymorphism with Alzheimer's disease
Journal article, 2010
The receptor for advanced glycation end-products (RAGE) has been implicated in several pathophysiological processes relevant to Alzheimer's disease (AD), including transport and synaptotoxicity of AD-associated amyloid beta (A beta) peptides. A recent Chinese study (Li et al. in J Neural Transm 117:97-104, 2010) suggested an association between the 82S allele of the functional single nucleotide polymorphism (SNP) G82S (rs2070600) in the RAGE-encoding gene AGER and risk of AD. The present study aimed to investigate associations between AGER, AD diagnosis, cognitive scores and cerebrospinal fluid AD biomarkers in a European cohort of 316 neurochemically verified AD cases and 579 controls. Aside from G82S, three additional tag SNPs were analyzed to cover the common genetic variation in AGER. The 82S allele was associated with increased risk of AD (P (c) = 0.04, OR = 2.0, 95% CI 1.2-3.4). There was no genetic interaction between AGER 82S and APOE epsilon 4 in producing increased risk of AD (P = 0.4), and none of the AGER SNPs showed association with A beta(42), T-tau, P-tau(181) or mini-mental state examination scores. The data speak for a weak, but significant effect of AGER on risk of AD.
contributes
circulating levels
product-specific receptor
end-products
cerebrospinal-fluid
SNP
amyloid-beta-protein
AGER
activation
receptor
synaptic plasticity
Advanced glycosylation end
Haplotype
Alzheimer's disease
secreted oligomers
rage
RAGE
advanced-glycation-endproducts
Author
Jonny Daborg
University of Gothenburg
Malin von Otter
University of Gothenburg
Annica Sjölander
University of Gothenburg
Staffan Nilsson
University of Gothenburg
Chalmers, Mathematical Sciences, Mathematical Statistics
L. Minthon
Lunds Universitet
Deborah Gustafson
University of Gothenburg
Ingmar Skoog
University of Gothenburg
Kaj Blennow
University of Gothenburg
Henrik Zetterberg
University of Gothenburg
Journal of Neural Transmission
03009564 (ISSN) 14351463 (eISSN)
Vol. 117 7 861-867Subject Categories (SSIF 2011)
Physiology
DOI
10.1007/s00702-010-0437-0