Alice Skoumalová

Blood markers of oxidative stress in Alzheimer's disease.

Alzheimer′s disease (AD) represents a highly common form of dementia, but can be diagnosed in the earlier stages before dementia onset. Early diagnosis is crucial for successful therapeutic intervention. The introduction of new diagnostic biomarkers for AD is aimed at detecting underlying brain pathology. These biomarkers reflect structural or biochemical changes related to AD. Examination of cerebrospinal fluid has many drawbacks; therefore, the search for sensitive and specific blood markers is ongoing. Investigation is mainly focused on upstream processes, among which oxidative stress in the brain is of particular interest. Products of oxidative stress may diffuse into the blood and evaluating them can contribute to diagnosis of AD. However, results of blood oxidative stress markers are not consistent among various studies, as documented in this review. To find a specific biochemical marker for AD, we should concentrate on specific metabolic products formed in the brain. Specific fluorescent intermediates of brain lipid peroxidation may represent such candidates as the composition of brain phospholipids is unique. They are small lipophilic molecules and can diffuse into the blood stream, where they can then be detected. We propose that these fluorescent products are potential candidates for blood biomarkers of AD.

The lipid peroxidation products as possible markers of Alzheimer's disease in blood.

Oxidative stress, which is present in Alzheimers disease (AD), results in the formation of various end-products of free radical reactions with proteins and lipids. At present there are no reliable diagnostic biomarkers of AD in the blood. Therefore, specific products of lipid peroxidation in the blood of AD patients were investigated. Lipophilic extracts of erythrocytes in the group of patients with AD (n = 44) and age-matched controls (n = 16) were studied. The end-products of lipid peroxidation, so called lipofuscin-like pigments (LFP), were analysed by fluorescence spectroscopy. It was found that the level of these products is significantly increased in erythrocytes of AD patients compared to controls. LFP were further separated by means of HPLC into individual fractions to study their composition in AD and controls. The specific fraction of LFP in AD patients, which was isolated, might represent a disease-specific product in the blood.

Hypercapnia protects erythrocytes against free radical damage induced by hypoxia in exposed rats

Several studies report that hypoxic exposure induces free radical oxidative damage in various tissues. The mechanism of this damage includes membrane lipid peroxidation which can be easily detected by measuring fluorescent end‐products of the process, i.e. lipofuscin‐like pigments. Four day exposure of rats to hypoxia (10% O2) increased the level of lipofuscin‐like pigments in erythrocytes up to 9 fold. This increase was completely prevented when the animals were exposed to hypercapnia (4.3% CO2) in addition to hypoxia. We studied the possible mechanism of the hypercapnic protection on isolated erythrocyte membranes in vitro. Lipid peroxidation was initiated by incubation of the membranes with iron ions and ascorbate. Production of malonaldehyde, the precursor of lipofuscin‐like pigments, was strongly inhibited in bicarbonate buffer. Similarly the production of lipofuscin‐like products was damped. These experiments suggest that the protective effect of hypercapnia might consist in direct interaction of CO2 with free radical processes. Copyright

End products of lipid peroxidation in erythrocyte membranes in Alzheimer's disease

Alzheimers disease (AD) is accompanied by oxidative stress in the brain. Because the brain tissue is rich in polyunsaturated fatty acids, it is prone to the free radical attack resulting in lipid peroxidation. Intermediates of lipid peroxidation may diffuse from the primary site, cross the blood–brain barrier and modify erythrocyte membranes in the bloodstream. We exposed isolated erythrocyte membranes from patients with AD and the control group to in vitro free radical damage and monitored the accumulation of the end products of lipid peroxidation, lipofuscin‐like pigments (LFPs), by fluorescence spectroscopy. LFPs were analyzed by means of tridimensional and synchronous fluorescence spectroscopy. The levels of LFP formed during in vitro peroxidation were significantly higher in erythrocyte membranes from patients with AD compared with the control group. Furthermore, the chemical composition of LFP in AD was different from the control group. The analysis of the specific modifications of erythrocyte membranes in AD is of great medical importance regarding the need of a diagnostic blood biomarker. Copyright

Analysis of lipophilic fluorescent products in blood of Alzheimer's disease patients

Alzheimers disease (AD) is a severe neurodegenerative disorder characterized by cognitive decline. Prodromal stage of AD, also called mild cognitive impairment (MCI), especially its amnestic type (aMCI), precedes dementia stage of AD. There are currently no reliable diagnostic biomarkers of AD in the blood. Alzheimers disease is accompanied by increased oxidative stress in brain, which leads to oxidative damage and accumulation of free radical reaction end‐products. In our study, specific products of lipid peroxidation in the blood of AD patients were studied. Lipophilic extracts of erythrocytes (AD dementia = 19, aMCI = 27, controls = 16) and plasma (AD dementia = 11, aMCI = 17, controls = 16) were analysed by fluorescence spectroscopy. The level of these products is significantly increased in erythrocytes and plasma of AD dementia and aMCI patients versus controls. We concluded that oxidative stress end‐products are promising new biomarkers of AD, but further detailed characterisation of these products is needed.

Corrigendum to “The lipid peroxidation products as possible markers of Alzheimer's disease in blood” [Experimental Gerontology 46 (2011) 38–42]

Corrigendum to “The lipid peroxidation products as possible markers of Alzheimers disease in blood” [Experimental Gerontology 46 (2011) 38–42] A. Skoumalova⁎, J. Ivica , P. Santorova, E. Topinkova, J. Wilhelm a Department of Medical Chemistry and Biochemistry, 2nd Faculty of Medicine Charles Universtity in Prague, Czech Republic b Department of Geriatrics, 1st Faculty of Medicine Charles University and General Faculty Hospital in Prague, Czech Republic