Plasma levels of soluble receptor for advanced glycation end products in Alzheimer's disease

Xu, Xiaoyan; Deng, Chao; Wang, Jian; Deng, Xiao‐Juan; Xiao, Qian; Li, Yuan; He, Qian; Fan, Wenhui; Quan, Fengying; Zhu, Yao-Ping; Cheng, Ping; Chen, Guojun

doi:10.1080/00207454.2016.1193861

Cited by 28 publications

(11 citation statements)

References 42 publications

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“…It can activate microglia and astrocytes in a reactive as well as in an inflammatory state, thus aggravating AD pathogenesis by inducing a cycle of inflammation and cellular stress [62]. In a cross-sectional clinical study of different dementia patient types, the levels of AGEs and its receptor RAGE were found upregulated in AD, whereas the levels of sRAGE were decreased, indicating that AGE, RAGE, and sRAGE might contribute to AD pathology [63].…”

Section: Implication Of Rage In Admentioning

confidence: 99%

Impact of HMGB1, RAGE, and TLR4 in Alzheimer’s Disease (AD): From Risk Factors to Therapeutic Targeting

Paudel

Angelopoulou

Piperi

et al. 2020

Cells

169

128

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Alzheimer’s disease (AD) is a devastating neurodegenerative disorder and a leading cause of dementia, with accumulation of amyloid-beta (Aβ) and neurofibrillary tangles (NFTs) as defining pathological features. AD presents a serious global health concern with no cure to date, reflecting the complexity of its pathogenesis. Recent evidence indicates that neuroinflammation serves as the link between amyloid deposition, Tau pathology, and neurodegeneration. The high mobility group box 1 (HMGB1) protein, an initiator and activator of neuroinflammatory responses, has been involved in the pathogenesis of neurodegenerative diseases, including AD. HMGB1 is a typical damage-associated molecular pattern (DAMP) protein that exerts its biological activity mainly through binding to the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4). RAGE and TLR4 are key components of the innate immune system that both bind to HMGB1. Targeting of HMGB1, RAGE, and TLR4 in experimental AD models has demonstrated beneficial effects in halting AD progression by suppressing neuroinflammation, reducing Aβ load and production, improving spatial learning, and inhibiting microglial stimulation. Herein, we discuss the contribution of HMGB1 and its receptor signaling in neuroinflammation and AD pathogenesis, providing evidence of its beneficial effects upon therapeutic targeting.

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Section: Implication Of Rage In Admentioning

confidence: 99%

Impact of HMGB1, RAGE, and TLR4 in Alzheimer’s Disease (AD): From Risk Factors to Therapeutic Targeting

Paudel

Angelopoulou

Piperi

et al. 2020

Cells

169

128

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“…Individuals with obesity, diabetes, or CI alone present with reduced circulating sRAGE profiles compared to lean healthy controls [ 26 – 29 ]. This evidence has led to the emergence of sRAGE as a suggested biological marker of both glucose tolerance status [ 29 ] and cognitive decline [ 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolic Derangements Contribute to Reduced sRAGE Isoforms in Subjects with Alzheimer’s Disease

Fuller

Miranda

Thyfault

et al. 2018

Mediators of Inflammation

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Although there is evidence for metabolic dysfunction and chronic inflammation in Alzheimer's disease (AD), circulating levels of soluble receptor for advanced glycation end products (sRAGE) and the receptor for advanced glycation end products (RAGE) ligand S100B have not been characterized. sRAGE is an important mediator in disease as it can act as a ligand decoy for RAGE and attenuate downstream inflammatory signaling. Cognitively healthy elderly and AD participants with and without type 2 diabetes (n = 135) were stratified according to the clinical dementia rating (CDR; 0 = normal cognition (NC); ≥0.5 = AD). Total serum sRAGE, endogenous secretory RAGE (esRAGE), and S100B were assayed via ELISAs, and cleaved RAGE (cRAGE) and the cRAGE : esRAGE ratio were calculated. cRAGE : esRAGE was lower in AD compared to NC (p < 0.05). Metabolic substratifications were used to investigate the factors that influence sRAGE pathology in AD. Stratification by BMI classification, median fat mass, median HOMA-IR, median insulin, and median amylin were all metabolic or anthropometric factors which significantly interacted with sRAGE profiles within AD subjects. There were no significant differences in serum S100B between groups. These characterizations of sRAGE contribute evidence to the link between impaired metabolism and cognitive decline due to AD.

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“…Thus maintaining high levels of circulating sRAGE isoforms is apparently advantageous for the organism (14,17,48). This is exemplified, in part, by data demonstrating that sRAGE isoforms are decreased in inflammatory conditions such as type 2 diabetes mellitus (T2DM), coronary artery disease, and neurodegenerative diseases (14,48,54), while treatment with recombinant sRAGE suppresses atherosclerosis and vascular dysfunction in animal models of diabetic coronary artery disease (34).…”

mentioning

confidence: 99%

Circulating soluble RAGE isoforms are attenuated in obese, impaired-glucose-tolerant individuals and are associated with the development of type 2 diabetes

Miranda

Somal

Mey

et al. 2017

American Journal of Physiology-Endocrinology and Metabolism

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The soluble receptor for advanced glycation end products (sRAGE) may be protective against inflammation associated with obesity and type 2 diabetes (T2DM). The aim of this study was to determine the distribution of sRAGE isoforms and whether sRAGE isoforms are associated with risk of T2DM development in subjects spanning the glucose tolerance continuum. In this retrospective analysis, circulating total sRAGE and endogenous secretory RAGE (esRAGE) were quantified via ELISA, and cleaved RAGE (cRAGE) was calculated in 274 individuals stratified by glucose tolerance status (GTS) and obesity. Group differences were probed by ANOVA, and multivariate ordinal logistic regression was used to test the association between sRAGE isoform concentrations and the proportional odds of developing diabetes, vs. normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). When stratified by GTS, total sRAGE, cRAGE, and esRAGE were all lower with IGT and T2DM, while the ratio of cRAGE to esRAGE (cRAGE:esRAGE) was only lower ( < 0.01) with T2DM compared with NGT. When stratified by GTS and obesity, cRAGE:esRAGE was higher with obesity and lower with IGT ( < 0.0001) compared with lean, NGT. In ordinal logistic regression models, greater total sRAGE (odds ratio, 0.91; < 0.01) and cRAGE (odds ratio, 0.84; < 0.01) were associated with lower proportional odds of developing T2DM. Reduced values of sRAGE isoforms observed with both obesity and IGT are independently associated with greater proportional odds of developing T2DM. The mechanisms by which each respective isoform contributes to obesity and insulin resistance may reveal novel treatment strategies for diabetes.

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Plasma levels of soluble receptor for advanced glycation end products in Alzheimer's disease

Abstract: Our results demonstrate that sRAGE may assist the diagnosis of AD from normal individuals, but cannot differentiate AD from VaD, MD or OD.

Cited by 28 publications

References 42 publications

Impact of HMGB1, RAGE, and TLR4 in Alzheimer’s Disease (AD): From Risk Factors to Therapeutic Targeting

Impact of HMGB1, RAGE, and TLR4 in Alzheimer’s Disease (AD): From Risk Factors to Therapeutic Targeting

Metabolic Derangements Contribute to Reduced sRAGE Isoforms in Subjects with Alzheimer’s Disease

Circulating soluble RAGE isoforms are attenuated in obese, impaired-glucose-tolerant individuals and are associated with the development of type 2 diabetes

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