Sign of lipid peroxidation as measured in the urine of patients with probable Alzheimer’s disease

Tuppo, Ehab; Forman, Lloyd J.; Spur, Bernd W.; Chan-Ting, R.E; Chopra, Anita; Cavalieri, Thomas A.

doi:10.1016/s0361-9230(01)00450-6

Cited by 79 publications

(35 citation statements)

References 21 publications

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“…8-iso-PGF2 ␣ is a useful marker of lipid peroxidation for the assessment of the OS condition [39,40] . A significant increase in 8-iso-PGF2 ␣ has been observed in the CSF [41] , plasma [42] , and urine [43,44] of AD patients, which is therefore similar to our present results. These data suggested that OS was associated with the pathogenesis of AD.…”

Section: Discussionsupporting

confidence: 92%

Effect of Vitamin E Administration on the Elevated Oxygen Stress and the Telomeric and Subtelomeric Status in Alzheimer’s Disease

Guan

Maeda

et al. 2011

Gerontology

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Background: Oxidative stress (OS) may be involved in the neurodegenerative process in Alzheimer’s disease (AD). Telomeres, the repeated sequences that cap chromosome ends, undergo shortening with each cell division, are sensitive to OS, and serve as markers of a cell’s replicative history. Telomere length shortening has been reported to relate to OS with aging process and aging-associated diseases, but the telomeric changes were not always identical, especially in change of telomere length distribution and subtelomeric methylation. The involvement of an OS-associated telomere change in the pathogenesis of AD has been discussed for decades, and the telomere length and telomerase activity were analyzed. However, other telomeric factors, such as the telomere distribution and subtelomeric methylation status, have not yet been analyzed. Objective: The subtelomeric methylation status as well as the telomere length were studied in AD with an antioxidant vitamin in terms of OS. Methods: We measured urinary 8-iso-PGF2α, a lipid-peroxidation product as an OS marker, and methylated and non-methylated telomere lengths in the peripheral blood mononuclear cells by Southern blotting in AD patients before and after vitamin E treatment. Results: The level of urinary 8-iso-PGF2α was found to have increased in AD. Middle-ranged telomeres (4.4–9.4 kb) increased and the shortest telomeres (<4.4 kb) decreased in AD patients. Telomeres were more methylated in both long telomeres and in short telomeres in AD compared with the control. The oral administration of the antioxidant vitamin E in 400 mg/day for 6 months in AD patients partly reversed AD-associated alterations in OS marker levels. Conclusions: AD patients showed an elevated OS marker level, and vitamin E lowered the OS level. In comparison with controls, AD patients showed shorter telomere lengths. Cells with short and long telomeres bore relatively hypermethylated subtelomeres in AD patients. Aging-associated accumulation of cells bearing short telomeres was not observed in AD. These results imply that long telomeres with hypomethylation tend to shorten faster, and cells bearing short telomeres with hypomethylation tend to more easily enter into a senescent state under elevated OS stress in AD. However, no significant effect on the altered telomeric profiles in AD patients could be detected after a 6-month administration of vitamin E.

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Section: Discussionsupporting

confidence: 92%

Effect of Vitamin E Administration on the Elevated Oxygen Stress and the Telomeric and Subtelomeric Status in Alzheimer’s Disease

Guan

Maeda

et al. 2011

Gerontology

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“…They are elevated in conditions associated with oxidative stress, including smoking, diabetes, heart disease, and AD. The isoprostane isoforms, iPF2␣-III and iPF2␣-VI, are elevated in AD patients (Montine et al, 1998;Pratico et al, 1998;Tuppo et al, 2001) as well as in patients with mild cognitive impairment, a prodromal phase of AD (Pratico et al, 2002). In addition, the Tg2576 mouse model of AD-like A␤ pathology (Hsiao et al, 1996), in which APP 695 with the Swedish familial mutation (APP sw ) is overexpressed, also shows elevated iPF2␣-VI levels before the onset of amyloid plaque formation (Pratico et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Thromboxane Receptor Activation Mediates Isoprostane-Induced Increases in Amyloid Pathology in Tg2576 Mice

Shineman¹,

Zhang²,

Leight³

et al. 2008

J. Neurosci.

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Alzheimer's disease (AD) amyloid plaques are composed of amyloid-␤ (A␤) peptides produced from proteolytic cleavage of amyloid precursor protein (APP). Isoprostanes, markers of in vivo oxidative stress, are elevated in AD patients and in the Tg2576 mouse model of AD-like A␤ brain pathology. To determine whether isoprostanes increase A␤ production, we delivered isoprostane iPF 2␣ -III into the brains of Tg2576 mice. Although treated mice showed increased brain A␤ levels and plaque-like deposits, this was blocked by a thromboxane (TP) receptor antagonist, suggesting that TP receptor activation mediates the effects of iPF 2␣ -III on A␤. This hypothesis was supported by cell culture studies that showed that TP receptor activation increased A␤ and secreted APP ectodomains. This increase was a result of increased APP mRNA stability leading to elevated APP mRNA and protein levels. The increased APP provides more substrate for ␣ and ␤ secretase proteolytic cleavages, thereby increasing A␤ generation and amyloid plaque deposition. To test the effectiveness of targeting the TP receptor for AD therapy, Tg2576 mice underwent long-term treatment with S18886, an orally available TP receptor antagonist. S18886 treatment reduced amyloid plaques, insoluble A␤, and APP levels, thereby implicating TP receptor signaling as a novel target for AD therapy.

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“…41 A search for a peripheral biomarker of oxidative damage in AD patients has been the focus of research by several groups in the last years. [42][43][44][45][46] A good biomarker could increase the diagnostic accuracy, help to identify mild cognitive impairment in subjects with risk to progress to AD and provide a useful monitor of pharmacological response. 44 The findings that both AD and mild cognitive impairment in patients showed an increase in the amount of oxidized DNA bases in peripheral cells when compared to controls are an indication that oxidative stress could be an earlier event in the pathogenesis of AD.…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E genotype is related to nitric oxide production in platelets

Marcourakis

Bahia

Kawamoto

et al. 2008

Cell Biochemistry & Function

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The presence of the epsilon4 allele of apolipoprotein E (APOE) is considered a risk factor for sporadic Alzheimer's disease (AD). Our recent data demonstrated that the systemic modulation of oxidative stress in platelets and erythrocytes is disrupted in aging and AD. In this study, the relationship between APOE genotype and oxidative stress markers, both in AD patients and controls, was evaluated. The AD group showed an increase in the content of thiobarbituric acid-reactive substances (TBARS) and in the activities of nitric oxide synthase (NOS) and Na, K-ATPase, when compared to controls. Both groups had a similar cGMP content and superoxide dismutase activity. APOE epsilon4 allele carriers showed higher NOS activity than non-carriers. These results suggest a possible influence of APOE genotype on nitric oxide (NO) production that might enhance the effects of age-related specific factor(s) associated with neurodegenerative disorders.

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Sign of lipid peroxidation as measured in the urine of patients with probable Alzheimer’s disease

Cited by 79 publications

References 21 publications

Effect of Vitamin E Administration on the Elevated Oxygen Stress and the Telomeric and Subtelomeric Status in Alzheimer’s Disease

Effect of Vitamin E Administration on the Elevated Oxygen Stress and the Telomeric and Subtelomeric Status in Alzheimer’s Disease

Thromboxane Receptor Activation Mediates Isoprostane-Induced Increases in Amyloid Pathology in Tg2576 Mice

Apolipoprotein E genotype is related to nitric oxide production in platelets

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