Neurofibrillary Tangles and Senile Plaques in Alzheimers Brains are Associated with Reduced Capillary Expression of Vascular Endothelial Growth Factor and Endothelial Nitric Oxide Synthase

John      Provias; Brian      Jeynes

Abstract

There is significant evidence to suggest that a dysfunctional blood-brain barrier [BBB] may contribute to the pathogenesis of some Alzheimers 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 [Aβ] 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 Aβ, 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.

Keywords: Blood-brain barrier, AD lesions, VEGF and eNOS positive capillaries

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