Abstract
The receptor for advanced glycation end products (RAGE) and its downstream pathways are involved in various inflammatory and immune responses. Importantly, there is soluble RAGE (sRAGE) that forms either by alternative splicing of RAGE messenger ribonucleic acid as the endogenous soluble form of RAGE (esRAGE) or by proteolytic cleavage of full-length RAGE protein. This study aimed to investigate the associations of the plasma levels of sRAGE and esRAGE in ischemic stroke (IS) patients with and without dementia. This cross-sectional study recruited patients with IS at a university medical center. Vascular dementia was defined as the scale of Clinical Dementia Ranking (CDR) ≥ 1. Standard enzyme-linked immunosorbent assay was used to measure the plasma concentration of sRAGE and esRAGE. From November 2014 to October 2015, a total of 172 IS patients (mean age: 72.1 ± 7.5 years, 64.5% male) were recruited, including 73 with CDR = 0, 63 with CDR = 0.5, and 36 with CDR ≥ 1. In univariate analysis, IS patients with dementia were older and had more diabetes mellitus, less atrial fibrillation, and higher post-stroke modified Rankin Scale scores than those without dementia. Plasma levels of sRAGE and esRAGE were significantly higher in IS patients with than those without dementia (1.44 ± 1.29 vs. 1.03 ± 0.48 and 0.39 ± 0.40 vs. 0.24 ± 0.13 ng/mL, both p < 0.01). Importantly, both parameters remained independent after adjustment for clinical variables (OR 2.683, p = 0.013 and OR 39.192, p = 0.006, respectively). In summary, plasma sRAGE and esRAGE were elevated in those with dementia compared with those without dementia among IS patients.
Highlights
Stroke is the third leading cause of death worldwide and the most frequent cause of permanent disabilities (Bhatnagar et al 2010)
Our results suggested that ischemic stroke (IS) patients with dementia had significantly higher levels of soluble RAGE (sRAGE) and endogenous soluble form of RAGE (esRAGE) compared to those without dementia
A review of the previous literature revealed that levels of serum or plasma sRAGE in patients with Vascular dementia (VD) had been investigated in only a few studies
Summary
Stroke is the third leading cause of death worldwide and the most frequent cause of permanent disabilities (Bhatnagar et al 2010). Stroke mortality has declined in recent years, the increased survival rates may translate into an increased number of cognitively impaired stroke patients (Pendlebury and Rothwell 2009). Neuromol Med (2017) 19:579–583 one of the most common causes of dementia. Whether there are certain post-stroke pathophysiological mechanisms involving the development of VD remains controversial (Thiel et al 2014; Pugazhenthi et al 2017). The receptor for advanced glycation end products (RAGE) is located on the plasma membrane of many types of cells including neurons (Alexiou et al 2010). A variety of ligands, including the advanced glycation end products (AGE), high-mobility group box 1 (HMGB1), binds to RAGE. Biological studies have demonstrated that sRAGE may have diverse roles reflecting the activation of cellular RAGE signaling and functioning as a decoy to compete with membrane RAGE for ligand binding (Lotze and Tracey 2005)
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