Significant negative correlations between capillary expressed eNOS and Alzheimer lesion burden.
Nitric oxide [NO] is known to have vasoregulatory, neuroprotective and blood-brain barrier (BBB) related transport functions in the human CNS. Altered NO levels are suspected of contributing to neurodegenerative disorders, including Alzheimer's disease (AD). NO is produced as a result of the activity of one or more of three isoforms of nitrogen oxide synthase (NOS). In this study we compared Alzheimer and normative comparison brain samples, from temporal and calcarine cortices, with respect to the interactive correlation between eNOS, iNOS and nNOS isoform positive capillaries and the presence of neurofibrillary tangles (NFTs) and senile plaques (SPs). Cortical samples were taken from the superior temporal and calcarine cortices of 10 confirmed AD and 10 non-demented comparison group (CG) brains. Contiguous coronal sections were stained using immunohistochemistry techniques to stain for tau protein, beta amyloid (A beta) n-termini ([40 and 42]), eNOS, iNOS and nNOS. The densities of NFTs, SPs, and eNOS, iNOS and nNOS positive capillaries were recorded. Non-parametric statistical analyses were applied to the data. Our results demonstrate a significant negative correlation between the presence of eNOS positive capillaries and NFTs and SPs in both cortices in AD brains. Our results support the view that eNOS activity should be targeted for further investigation, and that factors involved in the regulation of NO production may be amenable to therapeutic intervention.
Jeynes
Brian
B
Faculty of Applied Health Sciences, Brock University, St. Catharine's, Ontario, Canada. bjeynes@brocku.ca
Provias
John
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D002196:Capillaries / Q000201:enzymology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology*; D004730:Endothelium, Vascular / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis*; D058225:Plaque, Amyloid / Q000473:pathology; D012016:Reference Values
D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III