Circulating levels of soluble receptor for advanced glycation end products in Alzheimer disease and vascular dementia

Background: The receptor for advanced glycation end products (RAGE) is a cell surface receptor that has been implicated in vascular disease and neurodegeneration. Low levels of its secreted isoform, soluble RAGE (sRAGE), have been regarded as a putative risk factor for atherosclerosis. In addition, administration of sRAGE has been shown to reduce development of cerebral P-amyloidosis in an Alzheimer disease mouse model. Objective: To investigate the role of sRAGE as a biological marker for Alzheimer disease and vascular dementia. Design: Cross-sectional study of 152 patients with a clinical diagnosis of Alzheimer disease, 91 with vascular dementia and 161 control subjects. Main Outcome Measure: Plasma levels of sRAGE. Results: Levels of sRAGE were significantly reduced in the plasma of patients with Alzheimer disease compared with that for those with either vascular dementia (P <.05) or with controls (P <.001). Conclusions: Patients with Alzheimer disease have reduced levels of sRAGE in plasma compared with patients with vascular dementia and controls. The striking reduction of circulating sRAGE in Alzheimer disease further supports a role for the RAGE axis in this clinical entity and requires further investigation.