Expression of the receptor for advanced glycation end products in Huntington's disease caudate nucleus

Abstract

The accumulation of amyloid-beta and increased expression of its receptor RAGE (the receptor for advanced glycation end products) have been implicated in the pathogenesis of Alzheimer's disease (AD). Here we have used immunohistochemistry and double labelling to localize RAGE expression in Huntington's disease (HD) caudate nucleus (CN). Results showed that RAGE is expressed in at least two cell types in the CN, medium spiny projection neurons and astrocytes, with stronger staining in astrocytes than in neurons. The percentage of the total number of neurons positive for RAGE was significantly higher in G2 and G3 HD CN when compared with controls. What is more interesting however was the heterogeneous distribution of RAGE staining in CN. In controls, astrocytic RAGE staining was seen only in the superficial layer of the subependymal layer (SEL). In G1 HD cases, staining was seen throughout the entire width of SEL but extended into the CN in G2, 3 and 4. Neuronal RAGE staining was stronger in the medial CN than in the lateral CN in control and G1 cases. In G2, 3 and 4 cases, this staining gradient was not observed; more neuronal RAGE staining was however seen in the dorsal part of the CN when compared with the ventral part. The distribution of RAGE staining in neurons appeared to correlate with the ordered cell death seen in HD CN. Identification of the ligand for RAGE in HD brain and further functional studies are needed to clarify the role of RAGE in the pathogenesis of HD.