Evidence for altered LRP/RAGE expression in Alzheimer lesion pathogenesis.
There is significant evidence to suggest that a damaged or dysfunctional blood-brain barrier (BBB) may contribute to the pathogenesis of Alzheimer's disease (AD) lesions. Lipoprotein receptor-related protein (LRP-1) and receptor for advanced glycation end products (RAGE) are known to be important (BBB) capillary transport proteins. Altered expression of either of these capillary endothelial LRP-1 and RAGE receptor proteins could indicate a dysfunction of the BBB and its transport regulation of beta-amyloid (Abeta). Cortical samples from the superior temporal (ST) and calcarine occipital (COC) cortices of ten confirmed AD brains and ten comparison group (CG) brains were examined. The densities of neurofibrillary tangles (NFTs), senile plaques (SPs) and LRP-1 and RAGE positive capillaries were recorded and statistically analyzed. There was a statistically significant difference between AD and CG cases and the densities of LRP-1 and RAGE positive capillaries, the AD cases demonstrating the greater numbers. Further, in AD brains there were significant negative correlations between the Abeta burden of SPs and both LRP-1 and RAGE-positive capillaries [p < .001]. Additionally, there was a strong positive correlation between LRP-1 and RAGE capillaries in AD brains [p < .001]. These results suggest that alterations in the LRP-1 and RAGE mediated transport of Abeta take place in AD brains in lesion prone regions and may therefore contribute to SP lesion pathogenesis.
Faculty of Applied Health Sciences, Brock University, St. Catharine's, Ontario, Canada, L2S 3A1. bjeynes@brocku.ca
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D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D002352:Carrier Proteins; D005260:Female; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000502:physiology; D008875:Middle Aged
D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D017127:Glycation End Products, Advanced; D026503:Low Density Lipoprotein Receptor-Related Protein-1