Reduction in asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in the cerebrospinal fluid during aging and in patients with Alzheimer's disease

Abe, Takashi; Tohgi, Hideo; Murata, Tetsuya; Isobe, Chiaki; Sato, Chigumi

doi:10.1016/s0304-3940(01)02214-5

Cited by 55 publications

(34 citation statements)

References 21 publications

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“…We further confirm the finding of Abe et al [18] that CSF ADMA levels are decreased in AD. While in their study a 48% decrease was described, in our study the difference was -29.9% (95% CI 4.7 to -55.2), which is within a similar range.…”

Section: Discussionsupporting

confidence: 92%

“…Selley [17] observed markedly elevated ADMA plasma concentrations in a study with 25 patients suffering from AD and 25 matched controls. In cerebrospinal fluid (CSF), Abe et al [18] found lower ADMA levels in 15 AD patients as compared to 14 controls as well as a strong positive correlation of CSF ADMA levels and Mini Mental State Examination (MMSE) scores in their patients. In contrast to these findings stands a publication from Mulder et al [19] who reported data of a case-control study including 20 AD patients and 20 matched controls and did not observe any differences in CSF ADMA levels between both groups.…”

Section: Introductionmentioning

confidence: 99%

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Asymmetrical Dimethylarginine Is Increased in Plasma and Decreased in Cerebrospinal Fluid of Patients with Alzheimer’s Disease

Arlt¹,

Schulze

Eichenlaub³

et al. 2008

Dement Geriatr Cogn Disord

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Background: Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase and may alter NO production during pathological conditions. Concerning Alzheimer’s disease (AD), there are reports on altered cerebral NO metabolism, but only few studies on ADMA concentrations in plasma and cerebrospinal fluid (CSF). Methods: We assessed plasma ADMA in 80 AD patients and 80 age- and gender-matched controls and CSF ADMA in a subgroup of 53 AD patients and 20 controls. Results: ADMA plasma concentrations were increased, while CSF ADMA concentrations were decreased in AD patients. There was a significant association between decreasing CSF ADMA levels and the severity of cognitive impairment. Conclusion: Elevated ADMA in plasma might be a contributing factor for AD through alterations of NO metabolism, for example decreased cerebral microperfusion, while decreased levels of CSF ADMA might lead to a cerebral increase of NO, peroxynitrite production and oxidative protein damage. Our study reveals different mechanisms of plasma and CSF ADMA regulation, both potentially contributing to AD pathology.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Asymmetrical Dimethylarginine Is Increased in Plasma and Decreased in Cerebrospinal Fluid of Patients with Alzheimer’s Disease

Arlt¹,

Schulze

Eichenlaub³

et al. 2008

Dement Geriatr Cogn Disord

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“…The expression of dimethylargininase is dramatically increased in AD [65]. However, there are controversial reports regarding asymmetric dimethylarginine levels in AD [66,67]. The mRNA and protein levels of the enzyme argininosuccinate synthetase, the rate limiting enzyme in the metabolic pathway leading from L-citrulline to L-arginine (the physiological substrates of NOS), are significantly higher in glial cells of AD brain [68,69].…”

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confidence: 99%

Vascular oxidative stress in Alzheimer disease

Zhu

Smith

Honda

et al. 2007

Journal of the Neurological Sciences

159

156

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Alzheimer disease and cerebrovascular dementia are two common causes of dementia and, by present diagnostic criteria, are mutually exclusive using vascular pathology as an arbitrary demarcation in differential diagnosis. However, evidence from epidemiological, neuropathological, clinical, pharmacological, and functional studies suggest considerable overlap in risk factors and pathological changes suggesting shared common pathogenic mechanisms between these two diseases such that vascular factors play a vital role in the pathogenesis of Alzheimer disease. A high energy demand and lack of an endogenous fuel reserve make the brain highly dependent upon a continuous blood supply where disruption of cerebral blood vessels and blood flow can have serious consequences on neural activities. Indeed, many studies implicate metabolic defects in Alzheimer disease, such a reduced brain metabolism is one of the best documented abnormalities in the disease. Notably, since endothelial reactive oxygen species such as nitric oxide act as vasodilators at low concentrations, increased production coupled with elevated reactive oxygen species scavenging of nitric oxide, can lead to reduced bioavailability of nitric oxide and increased oxidative stress that damage sensitive vascular cells. In this respect, we and others have demonstrated that oxidative stress is one of the earliest pathological changes in the brain of Alzheimer disease patients and plays a critical role in the vascular abnormalities underlying metabolic defects in Alzheimer disease. Here, we discuss vascular factors in relation to Alzheimer disease and review hypoperfusion as a potential cause by triggering mitochondrial dysfunction and increased oxidative stress initiating the pathogenic process. KeywordsAlzheimer disease; hypoperfusion; mitochondria; nitric oxide; nitric oxide synthase; oxidative stress; vascular abnormalitiesCorrespondence to: George Perry, Ph.D., College of Sciences, University of Texas at San Antonio, 6900 North Loop 1604 West, San Antonio, Texas 78249-0661 USA, , george.perry@utsa.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. . Therefore, perivascular Aβ deposits may be a risk factor for reduced regional CBF [7]. Ultrastructural studies on blood vessels associated with Aβ deposits have shown their intermittent association with membrane abnormalities of smooth muscle cells [5]. Indeed, in AD cases with a clinical history of cerebral bleeding, the muscle layer is sometimes completely replaced by Aβ deposits, suggesting that the vascular system may be an initiator for the development of diseas...

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“…Chronic renal failure associated with hypertension [1,3,14,15] Stroke [16,17] Pulmonary hypertension [18][19][20] Left ventricular hypertrophy [21,22] Type II diabetes [23][24][25] Pre-eclampsia [26,27] Heart failure [28] Ischaemia [29,30] Hypercholesterolemia [31,32] Atherosclerosis [33,34] Alzheimers* [35,36] …”

Section: Cardiovascular Disorder Change In Adma Referencementioning

confidence: 99%

C-Reactive Protein and Asymmetric Dimethylarginine: Markers or Mediators in Cardiovascular Disorders?

Smith¹

2007

CPD

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This is an electronic version of an article published in Current Pharmaceutical Design, 13 (16). pp. [1619][1620][1621][1622][1623][1624][1625][1626][1627][1628][1629] 2007. The definitive version is available online at:http://www.bentham.org/cpd/index.htmThe WestminsterResearch online digital archive at the University of Westminster aims to make the research output of the University available to a wider audience. Copyright and Moral Rights remain with the authors and/or copyright owners. Users are permitted to download and/or print one copy for non-commercial private study or research. Further distribution and any use of material from within this archive for profit-making enterprises or for commercial gain is strictly forbidden.Whilst further distribution of specific materials from within this archive is forbidden, you may freely distribute the URL of WestminsterResearch.(http://www.wmin.ac.uk/westminsterresearch).In case of abuse or copyright appearing without permission e-mail wattsn@wmin.ac.uk. Abstract: C-reactive protein (CRP) has received much attention as a cardiovascular risk factor and has been recommended to be used in screening to assist in predicting the occurrence of cardiovascular disorders. There are numerous association studies documenting changes in circulating CRP concentrations, there are, however, fewer studies providing evidence that CRP mediates the progression of cardiovascular pathologies. Elucidating the potential mechanisms for CRP has been confounded by recent reports that contaminants of CRP are partially responsible for observed effects.In this review the use of CRP as a tool to predict cardiovascular disorders will be discussed alongside a more recently described cardiovascular risk factor asymmetric dimethylarginine (ADMA). An endogenously occurring nitric oxide synthase inhibitor, ADMA, is formed by the action of protein arginine methyltransferases and subsequent proteolysis and it is metabolised in vivo by the dimethylarginine dimethylaminohydrolases (DDAH). The evidence available documenting the effects of CRP and ADMA, the regulatory mechanisms and the genetic influences, will be discussed in order to determine whether CRP and ADMA are mediators in the progression of cardiovascular disorders or merely useful biomarkers.

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Reduction in asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in the cerebrospinal fluid during aging and in patients with Alzheimer's disease

Cited by 55 publications

References 21 publications

Asymmetrical Dimethylarginine Is Increased in Plasma and Decreased in Cerebrospinal Fluid of Patients with Alzheimer’s Disease

Asymmetrical Dimethylarginine Is Increased in Plasma and Decreased in Cerebrospinal Fluid of Patients with Alzheimer’s Disease

Vascular oxidative stress in Alzheimer disease

C-Reactive Protein and Asymmetric Dimethylarginine: Markers or Mediators in Cardiovascular Disorders?

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