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

• Published in: Mediators of inflammation Vol. 2018; no. 2018; pp. 1 - 10
• Main Authors: Morris, J. K., Thyfault, John P., Miranda, Edwin R., Fuller, Kelly N. Z., Haus, Jacob M.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2018; Hindawi; John Wiley & Sons, Inc; Wiley
• Subjects: Advanced glycosylation end products; Advertising executives; Aged; Alzheimer Disease - metabolism; Alzheimer's disease; Amylin; Body fat; Body mass index; Brain research; Cell adhesion & migration; Cognitive ability; Comorbidity; Dementia; Dementia disorders; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Fasting; Female; Geriatrics; Glycation End Products, Advanced - metabolism; Glycosylation; Humans; Inflammation; Insulin; Insulin - metabolism; Insulin resistance; Isoforms; Ligands; Male; Medical research; Medicine, Experimental; Metabolism; Neurochemistry; Obesity; Oxidative stress; Protein Isoforms - metabolism; Proteins; Receptor for Advanced Glycation End Products - metabolism; S100 Calcium Binding Protein beta Subunit - metabolism; S100b protein; Signal transduction; Type 2 diabetes; Kansas
• ISSN: 0962-9351; 1466-1861; 1466-1861
• DOI: 10.1155/2018/2061376

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.