Association of the RAGE G82S polymorphism with Alzheimer’s disease

• Published in: Journal of Neural Transmission Vol. 117; no. 7; pp. 861 - 867
• Main Authors: Daborg, Jonny, von Otter, Malin, Sjölander, Annica, Nilsson, Staffan, Minthon, Lennart, Gustafson, Deborah R., Skoog, Ingmar, Blennow, Kaj, Zetterberg, Henrik
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.07.2010; Springer Nature B.V
• Subjects: activation; Advanced glycosylation end; advanced-glycation-endproducts; Aged; AGER; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - genetics; Alzheimer Disease - psychology; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; amyloid-beta-protein; Apolipoprotein E4 - genetics; Biomarkers - cerebrospinal fluid; Case-Control Studies; cerebrospinal-fluid; circulating levels; Clinical Medicine; Cohort Studies; contributes; Dementias - Original; Dementias - Original Article; end-products; Europe; Female; Fysiologi; Genetic Association Studies; Genotype; Haplotype; Humans; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Neurologi; Neurology; Neuropsychological Tests; Neurosciences; Peptide Fragments - cerebrospinal fluid; Phosphorylation; Physiology; Polymorphism, Single Nucleotide; product-specific receptor; Psychiatry; RAGE; receptor; Receptor for Advanced Glycation End Products; Receptors, Immunologic - genetics; Risk; secreted oligomers; Sequence Analysis, DNA; SNP; synaptic plasticity; tau Proteins - cerebrospinal fluid; tau Proteins - metabolism; RAGE; Alzheimer’s disease; SNP; Advanced glycosylation end product-specific receptor; Haplotype
• ISSN: 0300-9564; 1435-1463; 1435-1463
• DOI: 10.1007/s00702-010-0437-0

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 β (Aβ) 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 ε4 in producing increased risk of AD ( P  = 0.4), and none of the AGER SNPs showed association with Aβ 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.