title: 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.
abstract: 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.
authors.affiliation: Department of Pathology and Molecular Medicine (Neuropathology), Hamilton Health Sciences, McMaster University, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Provias
authors.forename: Brian
authors.initials: B
authors.lastname: Jeynes
mesh_terms: 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
chemical_list: 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