49
views
0
recommends
+1 Recommend
0 collections
    7
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          Receptor for advanced glycation end products (AGEs; RAGE) binds to both AGEs and amyloid-beta peptides. RAGE is involved in chronic complications of type 2 diabetes and Alzheimer’s disease. We aimed to investigate the roles of RAGE, AGEs and the Gly82Ser polymorphism of RAGE in mild cognitive impairment (MCI) among type 2 diabetes patients.

          Methods

          Of the 167 hospitalized type 2 diabetes patients recruited, 82 satisfied the diagnostic criteria for MCI, and 85 matched control individuals were classified as non-MCI. Demographic data were collected, and the soluble RAGE (sRAGE) concentrations, serum AGE-peptide (AGE-P) levels, RAGE Gly82Ser genotype and neuropsychological test results were examined.

          Results

          The MCI group exhibited a decreased sRAGE level (0.87±0.35 vs. 1.05±0.52 ng/ml, p<0.01) and an increased serum AGE-P level (3.54±1.27 vs. 2.71±1.18 U/ml, p<0.01) compared with the control group. Logistic regression analysis indicated that each unit reduction in the sRAGE concentration increased the MCI risk by 54% (OR 0.46[95% CI 0.22–0.96], p = 0.04) and that each unit increase in the AGE-P level increased the MCI risk by 72% in the type 2 diabetes patients (OR 1.72[95% CI 1.31–2.28], p<0.01). The serum sRAGE level was negatively correlated with the score on the trail making test-B (TMT-B) (r = -0.344, p = 0.002), which indicates early cognitive deficits related to diabetes. Moreover, the AGE-P level was positively correlated with multiple cognitive domains (all p<0.05). No significant differences in the neuropsychological test results or serum RAGE concentrations between the different RAGE genotypes or in the RAGE genotype frequencies between the MCI and control groups were identified (all p>0.05).

          Conclusions

          The RAGE pathway partially mediates AGE-induced MCI in diabetic patients. The serum AGE-P level may serve as a serum biomarker of MCI in these individuals, and sRAGE represents a predictor and even a potential intervention target of early cognitive decline in type 2 diabetes patients.

          Trial registration

          Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis ChiCTR-OCC-15006060

          Related collections

          Most cited references41

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Hardy-Weinberg Equilibrium Testing of Biological Ascertainment for Mendelian Randomization Studies

          Mendelian randomization (MR) permits causal inference between exposures and a disease. It can be compared with randomized controlled trials. Whereas in a randomized controlled trial the randomization occurs at entry into the trial, in MR the randomization occurs during gamete formation and conception. Several factors, including time since conception and sampling variation, are relevant to the interpretation of an MR test. Particularly important is consideration of the “missingness” of genotypes that can be originated by chance, genotyping errors, or clinical ascertainment. Testing for Hardy-Weinberg equilibrium (HWE) is a genetic approach that permits evaluation of missingness. In this paper, the authors demonstrate evidence of nonconformity with HWE in real data. They also perform simulations to characterize the sensitivity of HWE tests to missingness. Unresolved missingness could lead to a false rejection of causality in an MR investigation of trait-disease association. These results indicate that large-scale studies, very high quality genotyping data, and detailed knowledge of the life-course genetics of the alleles/genotypes studied will largely mitigate this risk. The authors also present a Web program (http://www.oege.org/software/hwe-mr-calc.shtml) for estimating possible missingness and an approach to evaluating missingness under different genetic models.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Mild cognitive impairment (MCI) in medical practice: a critical review of the concept and new diagnostic procedure. Report of the MCI Working Group of the European Consortium on Alzheimer's Disease.

            Mild cognitive impairment (MCI) was proposed as a nosological entity referring to elderly people with mild cognitive deficit but no dementia. MCI is a heterogeneous clinical entity with multiple sources of heterogeneity. The concept of MCI was reviewed and a diagnostic procedure with three different stages was proposed by the European Consortium on Alzheimer's Disease Working Group on MCI. Firstly, MCI should correspond to cognitive complaints coming from the patients or their families; the reporting of a relative decline in cognitive functioning during the past year by a patient or informant; cognitive disorders as evidenced by clinical evaluation; absence of major repercussions on daily life; and absence of dementia. These criteria, similar to those defined during an international workshop in Stockholm, make it possible to identify an MCI syndrome, which is the first stage of the diagnostic procedure. Secondly, subtypes of MCI had to be recognised. Finally, the aetiopathogenic subtype could be identified. Identifying patients at a high risk for progression to dementia and establishing more specific and adapted therapeutic strategies at an early stage, together with more structured overall management, is made possible by the diagnostic procedure proposed.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Identification, classification, and expression of RAGE gene splice variants.

              The receptor for advanced glycation end-products (RAGE) is a single-transmembrane, multiligand receptor of the immunoglobulin superfamily. RAGE up-regulation is implicated in numerous pathological states including vascular disease, diabetes, cancer, and neurodegeneration. The understanding of the regulation of RAGE is important in both disease pathogenesis and normal homeostasis. Here, we demonstrate the characterization and identification of human RAGE splice variants by analysis of RAGE cDNA from tissue and cells. We identified a vast range of splice forms that lead to changes in the protein coding region of RAGE, which we have classified according to the Human Gene Nomenclature Committee (HGNC). These resulted in protein changes in the ligand-binding domain of RAGE or the removal of the transmembrane domain and cytosolic tail. Analysis of splice variants for premature termination codons reveals approximately 50% of identified variants are targeted to the nonsense-mediated mRNA decay pathway. Expression analysis revealed the RAGE_v1 variant to be the primary secreted soluble isoform of RAGE. Taken together, identification of functional splice variants of RAGE underscores the biological diversity of the RAGE gene and will aid in the understanding of the gene in the normal and pathological state.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                8 January 2016
                2016
                : 11
                : 1
                : e0145521
                Affiliations
                [1 ]Department of Endocrinology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, PR China
                [2 ]Department of the Intensive Care Unit, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu, Sichuan Province, PR China
                University of Pittsburgh, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: SW PW. Performed the experiments: PW RH SL WX RC HS. Analyzed the data: PW RH SL WX RC HS. Contributed reagents/materials/analysis tools: SW PW. Wrote the paper: PW SL SW.

                [¤]

                Current address: Department of Endocrinology, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, East District, Chengdu, Sichuan Province, PR China

                ‡ This author is first author on this work.

                Article
                PONE-D-15-24342
                10.1371/journal.pone.0145521
                4706319
                26745632
                72f23514-c279-4c64-89a6-6a5a3d0f97d7
                © 2016 Wang et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 June 2015
                : 5 December 2015
                Page count
                Figures: 1, Tables: 5, Pages: 15
                Funding
                This work was partially supported by the National Natural Science Foundation of China ( http://www.nsfc.gov.cn/ No.81370921, Wang SH; and No.81570732, Wang SH); the Social Development Project of JiangSu Province ( http://www.jstd.gov.cn/ No.SBE201170735, Wang SH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article