REDUCED RAGE mRNA IN MONONUCLEAR BLOOD CELLS OF PATIENTS WITH PROBABLE ALZHEIMER DISEASE

The precise pathophysiology of Alzheimer disease (AD) remains obscure, though there is growing evidence that interaction of amyloid-beta (Aβ) peptide with the receptor for advanced glycation end-products (RAGE) contributes to the neuronal degeneration–death characterizing the disorder. Immunohistochemical studies in AD brains show increased RAGE expression in vessels proximal to senile plaques,¹ probably resulting in enhanced Aβ transport across the blood–brain barrier.² In addition, activation of RAGE by Aβ concentrations >10 nM induces cellular stress and inflammatory cytokine production that may ultimately act neurotoxically.³

RAGE tissue expression under physiologic conditions is rather low, but marked upregulation is noted whenever its ligands accumulate in the extracellular space.⁴ Apart from neurons and glia, the receptor is present in peripheral cell types⁵ (fibroblasts, endothelium, smooth muscle, peripheral blood mononuclear cells [PBMNC]). In these cells, RAGE gene transcripts undergo alternative splicing, resulting in distinct receptor isoforms that can be either transmembrane or soluble (sRAGE).⁶ Accordingly, we used PBMNCs as a peripheral model to evaluate possible abnormalities in total RAGE-mRNA expression in AD.