Soluble low density lipoprotein receptor-related protein-1 (sLRP) and the soluble form of the receptor for advanced glycation end products (sRAGE) may reflect some peripheral plasma features of the pathophysiological process of Alzheimer's disease (AD). Decreased plasma levels of sLRP and sRAGE in patients with AD have been documented. However, whether different levels of these proteins can differentiate AD from other types of dementia has not been described. In the present study we assessed the concentrations of these two proteins in 126 patients with AD, 96 with vascular dementia (VaD), 30 with non-AD neurodegenerative dementias (NND) and 98 cognitively normal controls (NC). Plasma sLRP was significantly lower in the group with AD compared with any of the other three groups (p < 0.001). Sensitivity of sLRP was 77.8% for AD, whereas specificity was 93.3% for NND, 85.7% for the NC and 58.3% for those with VaD. Plasma sRAGE showed a significantly lower concentration in the group with AD compared with those in the VaD or NC group, but there were no significant differences between the AD compared to the NND group or the VaD compared to the NND group. Sensitivity of sRAGE was 82.5% for patients with AD, whereas specificity was 53.5% for NND, 73.5% for the NC group and 43.8% for those with VaD. The receiving operator characteristic analysis of combined sLRP and sRAGE showed a higher diagnostic accuracy (area under the curve, 0.88; 95% confidence interval, 0.84-0.93) than that of either sLRP or sRAGE considered singly. The results support the possibility that these two biomarkers may help with the diagnosis of AD. (C) 2012 Elsevier Ltd. All rights reserved.