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Enzo Emanuele, MD; Angela D’Angelo, PhD; Carmine Tomaino, PhD; Giuliano Binetti, MD; Roberta Ghidoni, PhD; Pierluigi Politi, MD; Livia Bernardi, PhD; Raffaele Maletta, MD; Amalia C. Bruni, MD; Diego Geroldi, MD

Arch Neurol. 2005;62:1734-1736.

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 -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.

Author Affiliations: Molecular Medicine Laboratory (Dr Emanuele), Department of Internal Medicine and Medical Therapeutics (Drs Geroldi and D’Angelo), and Department of Psychiatry (Dr Politi), University of Pavia, IRCCS San Matteo Hospital, Pavia, Italy; Regional Neurogenetic Centre AS6, Lamezia Terme, Italy (Drs Tomaino, Bernardi, Maletta, and Bruni); Memory Clinic, NeuroBioLab, IRCCS Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy (Drs Binetti and Ghidoni).