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.
Faculty of Applied Health Sciences, Brock University, St. Catharine's, Ontario, Canada. bjeynes@brocku.ca
Brian
B
Jeynes
John
J
Provias
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D002196:Capillaries / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic