Plasma antioxidant status, immunoglobulin G oxidation and lipid peroxidation in demented patients:Relevance to Alzheimer disease and vascular dementia

A large body of evidence supports a role of oxidative stress in Alzheimer disease (AD) and in cerebrovascular disease. A vascular component might be critical in the pathophysiology of AD, but there is a substantial lack of data regarding the simultaneous behavior of peripheral antioxidants and biomarkers of oxidative stress in AD and vascular dementia (VaD). Sixty-three AD patients, 23 VaD patients and 55 controls were included in the study. We measured plasma levels of water-soluble (vitamin C and uric acid) and lipophilic (vitamin E, vitamin A, carotenoids including lutein, zeaxanthin, β-cryptoxanthin, lycopene, α- and β-carotene) antioxidant micronutrients as well as levels of biomarkers of lipid peroxidation [malondialdehyde (MDA)] and of protein oxidation [immunoglobulin G (IgG) levels of protein carbonyls and dityrosine] in patients and controls. With the exception of β-carotene, all antioxidants were lower in demented patients as compared to controls. Furthermore, AD patients showed a significantly higher IgG dityrosine content as compared to controls. AD and VaD patients showed similar plasma levels of plasma antioxidants and MDA as well as a similar IgG content of protein carbonyls and dityrosine. We conclude that, independent of its nature - vascular or degenerative - dementia is associated with the depletion of a large spectrum of antioxidant micronutrients and with increased protein oxidative modification. This might be relevant to the pathophysiology of dementing disorders, particularly in light of the recently suggested importance of the vascular component in AD development. Copyright © 2004 S. Karger AG, Basel.

P4-235 protein oxidation, lipid peroxidation and antioxidant status are similarly altered in Alzheimer disease and vascular dementia

Background: A large body of evidence supports a role of oxidative stress in Alzheimer disease (AD) and in cerebrovascular disease. A vascular component might be critical in the pathophysiology of AD. Objective(s): To evaluate the simultaneous behavior of a broad spectrum of peripheral antioxidants and biomarkers of oxidative stress in AD and vascular dementia (VaD). Methods: Sixty-three AD patients, 23 VaD patients and 55 controls were included in the study. We measured plasma levels of water-soluble (vitamin C and uric acid) and lipophilic (vitamin E, vitamin A, carotenoids including lutein, zeaxanthin, [3-cryptoxanthin, lycopene, c~- and [3-carotene) antioxidant micronutrients as well as levels of biomarkers of lipid peroxidation [malondialdehyde (MDA)] and of protein oxidation [immunoglobniin G (Ig G) levels of protein carbonyls and dityrosine] in patients and controls. Results: AD and VaD patients showed significantly decreased plasma levels of the water-soluble vitamin C and uric acid, of the lipophilic vitamin Eand vitamin A, and of the carotenoids lutein, zeaxanthin, 13-cryptoxanthin, lycopene and (x-carotene as compared to controls; among biomarkers of oxidative stress, only the content of dityrosine in Ig G was found to be significantly higher (p < 0.01) in AD patients as compared to controls; although a trend towards higher levels of dityrosine was also observed in VaD subjects compared to controls (6.3 4- 1.7 ~M in VaD patients vs. 5.1 4- 1.6 IxM in controls; p = 0.06), it did not reach statistical significance. In a cumulative analysis of all patient samples, a significant inverse association was found between plasma lycopene and MDA levels (r = -0.53, p < 0.0001). Conclusions: Independent of its nature-vascular or degenerativedementia is associated with the depletion of a large spectrum of antioxidant micronutrients and with increased protein oxidative modification. This might be relevant to the pathophysiology of dementing disorders, particularly in light of the recently suggested importance of the vascular component in AD development.

Creutzfeldt-Jakob disease and vision

This review describes a group of diseases known as the transmissible spongiform encephalopathies (TSEs), which affect animals and humans. Examination of affected brain tissue suggests that these diseases are caused by the acquisition and deposition of prion protein (PrP). Creutzfeldt-Jakob disease (CJD) is the most important form of TSE in humans with at least four different varieties of the disease. Variant CJD (vCJD), a new form of the disease found in the UK, has several features that differ from the classical forms including early age of onset, longer duration of disease, psychiatric presentation (for example, depression) and extensive florid plaque development in the brain. About 10 per cent of patients with CJD exhibit visual symptoms at disease presentation and approximately 50 per cent during the course of the disease. The most commonly reported visual symptoms include diplopia, supranuclear palsies, complex visual disturbances, homonymous visual field defects, hallucinations and cortical blindness. Saccadic and smooth pursuit movements appear to be more rarely affected. The agent causing vCJD accumulates in lymphoid tissue such as the spleen and tonsils. The cornea has lymphoid tissue in the form of corneal dendritic cells that are important in the regulation of the immune response in the anterior segment of the eye. The presence of these cells in the cornea has raised the possibility of transmission between patients via optical devices that contact the eye. Although such transmission is theoretically possible it remains highly improbable.

Size frequency distributions of abnormal protein deposits in Alzheimer’s disease and variant Creutzfeldt-Jakob disease

TThe size frequency distributions of ß-amyloid (Aß) and prion protein (PrPsc) deposits were studied in Alzheimer’s disease (AD) and the variant form of Creutzfeldt-Jakob disease (vCJD) respectively. All size distributions were unimodal and positively skewed. Aß deposits reached a greater maximum size and their distributions were significantly less skewed than the PrPsc deposits. All distributions were approximately log-normal in shape but only the diffuse PrPsc deposits did not deviate significantly from a log-normal model. There were fewer larger classic Aß deposits than predicted and the florid PrPsc deposits occupied a more restricted size range than predicted by a log-normal model. Hence, Aß deposits exhibit greater growth than the corresponding PrPsc deposits. Surface diffusion may be particularly important in determining the growth of the diffuse PrPsc deposits. In addition, there are factors limiting the maximum size of the Aß and florid PrPsc deposits.

Do β-amyloid (Aβ) deposits in patients with Alzheimer's disease and Down's syndrome grow according to the log-normal model?

The size frequency distributions of diffuse, primitive and classic β- amyloid (Aβ) deposits were studied in single sections of cortical tissue from patients with Alzheimer's disease (AD) and Down's syndrome (DS) and compared with those predicted by the log-normal model. In a sample of brain regions, these size distributions were compared with those obtained by serial reconstruction through the tissue and the data used to adjust the size distributions obtained in single sections. The adjusted size distributions of the diffuse, primitive and classic deposits deviated significantly from a log-normal model in AD and DS, the greatest deviations from the model being observed in AD. More Aβ deposits were observed close to the mean and fewer in the larger size classes than predicted by the model. Hence, the growth of Aβ deposits in AD and DS does not strictly follow the log-normal model, deposits growing to within a more restricted size range than predicted. However, Aβ deposits grow to a larger size in DS compared with AD which may reflect differences in the mechanism of Aβ formation.