An investigation into the role of P-glycoprotein in Alzheimer's disease lesion pathogenesis

The pathogenesis of Alzheimer's disease (AD) senile plaque (SP) and neurofibrillary tangle (NFT) lesions putatively involves a compromised blood-brain barrier (BBB). P-glycoprotein (P-gp) is a recognized BBB-related efflux transporter protein. In this investigation we determined the density of SP and NFT lesions and capillary densities stained positively for P-glycoprotein (P-gp), and other transport proteins, in AD and control group (CG) brain samples. Our results indicate that there are significant negative correlations (p < .01) between the densities of NFT and SP(40) lesions and P-gp positive capillaries in AD but not CG brain samples. Significant positive correlations (p < .01) were observed between the densities of P-gp positive capillaries and LRP and RAGE positive capillaries in both AD and CG brains. These results also suggest that the levels of capillary P-gp may contribute to AD lesion development and that the role of P-gp is associated with that of LRP and RAGE. (C) 2010 Elsevier Ireland Ltd. All rights reserved.