Neurofibrillary tangles and senile plaques in Alzheimer's brains are associated with reduced capillary expression of vascular endothelial growth factor and endothelial nitric oxide synthase.
There is significant evidence to suggest that a dysfunctional blood-brain barrier [BBB] may contribute to the pathogenesis of some Alzheimer's disease [AD] lesions. An indicator for this could be diminished capillary vascular endothelial growth factor [VEGF] and / or endothelial nitric oxide synthase [eNOS] activity in AD brains. Cortical samples were taken from the superior temporal and calcarine cortices of ten confirmed AD and ten non-demented comparison brains. Contiguous coronal sections were stained using immunohistochemistry techniques to stain for tau protein, beta-amyloid [Abeta] n-termini ([40 & 42]), VEGF and eNOS. Standardized regions of cortex were randomly selected. Areas of ten contiguous field-diameters of comparable and full cortical widths were observed in each section and the densities of neurofibrillary tangles [NFTs], senile plaques [SPs] and Abeta, VEGF and eNOS positive capillaries were recorded. In both AD cortices there were significant inverse correlations found between both VEGF and eNOS-positive microvessels and the presence of NFTs, and each of the amyloid isoforms in SPs and amyloid-positive capillaries [p < 0.01]. In addition there was a significant positive correlation between VEGF and eNOS densities in both cortices [p< 0.01].These results suggest that diminished VEGF and eNOS activity in particularly lesion prone regions of AD brains may contribute to the pathogenesis of NFT and / or SP lesions.
Provias
John
J
Department of Pathology and Molecular Medicine (Neuropathology), Hamilton Health Sciences, McMaster University, Ontario, Canada.
Jeynes
Brian
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002196:Capillaries / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016875:tau Proteins; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III