Significant negative correlations between capillary expressed eNOS and Alzheimer lesion burden

Jeynes, Brian; Provias, John

doi:10.1016/j.neulet.2009.07.091

Cited by 47 publications

(32 citation statements)

References 27 publications

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“…There is evidence that pharmacological or genetic inactivation of eNOS in cultured brain microvascular endothelial cells increase the expression of A PP and -site A PP cleaving enzyme 1 (BACE-1), as well as A production [96]. Consistently with these findings, other studies [97,98] have shown an inverse correlation between eNOS-positive capillaries and A senile plaques in cortical samples of AD brains.…”

Section: No-mediated Disruption Of Microvascular Homeostasismentioning

confidence: 64%

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Marco

Venneri

Farkas

et al. 2015

Neurobiology of Disease

232

185

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Article available under the terms of the CC-BY-NC-ND licence (https://creativecommons.org/licenses/by-nc-nd/4.0/) eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request.

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Section: No-mediated Disruption Of Microvascular Homeostasismentioning

confidence: 64%

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Marco

Venneri

Farkas

et al. 2015

Neurobiology of Disease

232

185

View full text Add to dashboard Cite

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“…37 In addition, in a large memory clinic cohort, amyloid deposition in those with small vessel disease was most aggravated in APOEε4 carriers. 30 Associations between vasoreactivity and dementia remained similar overall, and became stronger for APOEε4 carriers after adjustment for traditional cardiovascular risk factors. Conversely, the associations of cardiovascular risk factors with the risk of dementia were broadly unchanged by adjustment for vasoreactivity.…”

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

“…29 Interestingly, nitric oxide has also been shown to modulate expression of amyloid precursor protein and β-site amyloid precursor protein-cleaving enzyme 1 in mice. 29 Endothelial nitric oxide synthase levels correlate well with τ and amyloid burden in patients with AD, 30 further suggesting a role of endothelial dysfunction in dementia.Our results suggest that the association between cerebral microvascular function and cognition is more profound in carriers of the APOEε4 allele, the major genetic risk factor for AD.31 This is in line with a recent cross-sectional study, that found the impact of APOEε4 on cognition to be amplified in the presence of impaired vasoreactivity. 32 As imaging markers of both microvascular disease and cognitive function, such as white matter lesions and microbleeds, 9,33 are abundant in APOEε4 carriers, 34 specific APOE-related mechanisms may account for these observations.…”

mentioning

confidence: 99%

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Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia

Wolters

Bruijn

Hofman

et al. 2016

ATVB

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A bout 44 million people worldwide are living with dementia, and because of a rapidly aging population this number is predicted to nearly double every 20 years until 2050. 1,2 Consequently, the social and economic burden of dementia will increase enormously, unless preventive or curative measures can be established. Cardiovascular health is increasingly acknowledged as a key determinant in prevention of dementia, including Alzheimer disease (AD).3,4 Yet, the mechanism by which vascular damage leads to cognitive decline remains largely unknown.Although many studies have related cognitive function to static markers of cerebrovascular pathology, such as small vessel disease on magnetic resonance imaging and the retinal vasculature, few provide a functional measure of cerebral vascular disease. Cerebral vasoreactivity (CVR) reflects the ability of the cerebral arterioles and capillaries to dilate in response to increased neuronal metabolic demand, 5 and can be quantified in vivo using transcranial Doppler (TCD) or magnetic resonance imaging. Vasoreactivity is essential for maintenance of continuous cerebral perfusion, and impaired vasoreactivity is associated with (cardiovascular) mortality in the general population 6 and risk of stroke in the presence of flow-limiting carotid artery stenosis. 7 In addition, lower vasoreactivity correlates with higher volumes of cerebral white matter lesions, 8 which are strongly associated with cognitive decline and dementia.9 Several small cross-sectional studies have found CVR to be reduced in patients with dementia or mild cognitive impairment compared with healthy controls, 10-12 but its impact on cognitive decline and the risk of dementia is uncertain.We hypothesized that impaired CVR precedes dementia, and aimed to determine the association of CVR with cognitive decline and the risk of dementia in a population-based study.© 2015 American Heart Association, Inc. Materials and MethodsThis study is embedded within the Rotterdam study, an ongoing population-based cohort study in The Netherlands. TCD investigation with induction of hypercapnia was added to the core protocol for the second follow-up examination, from July 1997 to December 1999. Materials and Methods are available in the online-only Data Supplement. ResultsAmong 2569 eligible participants undergoing TCD with induced hypercapnia, no temporal bone window was present on either side in 632 (24.6%) individuals. Measurements could not be completed in 214 (8.3%) cases because of participants feeling anxious or unwell (n=54), lack of time (n=3), or other undocumented causes (n=157). In addition, in 94 participants we failed to obtain a reliable measurement of CVR despite adequate CO 2 induction, thus leaving a total of 1629 cases for analysis. Baseline characteristics of participants in comparison with nonparticipants are shown in Table 1. CVR was strongly impaired in current smokers and to a lesser extent in participants with a history of hypertension or diabetes mellitus. Conversely, higher systolic and diastoli...

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“…Altered NO levels are suspected of contributing to neurodegenerative disorders, including Alzheimer's disease (AD) [11]. Nitrotyrosine which has been found in patients with AD was highly co-localized with nNOS in cortical pyramidal cells [12].…”

Section: Introductionmentioning

confidence: 99%

Nitric Oxide Production during Cerebral Ischemia and Reperfusion in eNOS- and nNOS-Knockout Mice

Ito

Ohkubo²,

Asano³

et al. 2010

CNR

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The purpose of this study was to clarify the kinetics of nitric oxide (NO) induced by either endothelial NO synthase (eNOS) or neuronal NO synthase (nNOS) after transient global forebrain ischemia. We investigated NO production and ischemic changes to hippocampal CA1 neurons in eNOS knockout (-/-) mice and nNOS (-/-) mice during cerebral ischemia and reperfusion. NO production was continuously monitored by in vivo microdialysis. Global forebrain ischemia was produced by occlusion of both common carotid arteries for 10 minutes. Levels of nitrite (NO(2)(-)) and nitrate (NO(3)(-)), as NO metabolites, in dialysate were determined using the Griess reaction. Two hours after the start of reperfusion, animals were perfused with 4% paraformaldehyde. Hippocampal CA1 neurons were divided into three phases (severely ischemic, moderately ischemic, surviving), and the ratio of surviving neurons to degenerated neurons was calculated as the survival rate. The relative cerebral blood flow (rCBF) was significantly higher in nNOS (-/-) mice than in control mice after reperfusion. Levels of NO(3)(-) were significantly lower in eNOS (-/-) mice and nNOS (-/-) mice than in control mice during ischemia and reperfusion. NO(3)(-) levels were significantly lower in nNOS (-/-) mice than in eNOS (-/-) mice after the start of reperfusion. Survival rate tended to be higher in nNOS (-/-) mice than in control mice, but not significantly. These in vivo data suggest that NO production in the striatum after reperfusion is closely related to activities of both nNOS and eNOS, and is mainly related to nNOS following reperfusion.

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Significant negative correlations between capillary expressed eNOS and Alzheimer lesion burden

Cited by 47 publications

References 27 publications

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia

Nitric Oxide Production during Cerebral Ischemia and Reperfusion in eNOS- and nNOS-Knockout Mice

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