Alzheimer's 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.
- MeSH
- Alzheimerova nemoc metabolismus MeSH
- erytrocytární membrána metabolismus MeSH
- lidé MeSH
- lipofuscin metabolismus MeSH
- oxidační stres MeSH
- peroxidace lipidů MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
- MeSH
- Alzheimerova nemoc krev diagnóza patofyziologie MeSH
- antioxidancia analýza MeSH
- biologické markery krev MeSH
- lidé MeSH
- mozek metabolismus patofyziologie MeSH
- nukleové kyseliny metabolismus MeSH
- oxidační stres * MeSH
- peroxidace lipidů MeSH
- proteiny metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Alzheimerova choroba (ACH) se řadí mezi závažná neurodegenerativní onemocnění provázená oxidačním stresem. Produkty radikálových reakcí mohou difundovat z primárních míst a být detekovány v cerebrospinální tekutině (CSF) či krvi. Tyto produkty představují potenciální biochemické markery pro diagnostiku ACH. Nejvíce pozornosti je zaměřeno na analýzu CSF, protože odráží patologické změny v mozkové tkáni u ACH. V CSF byly potvrzeny zvýšené hladiny oxidačních produktů lipidů i proteinů. Hladiny vitaminů jsou snížené, nicméně existují i práce, které nenašly rozdíly oproti kontrolám. Některé studie se zaměřily na detekci produktů oxidačního stresu v krvi u ACH, ale výsledky nejsou konzistentní. Část prací ukazuje na nárůst oxidačních produktů a snížené hladiny antioxidantů v plazmě. Nicméně jiné práce tyto výsledky nepotvrdily. Z hlediska hledání diagnostického biomarkeru pro ACH má význam se zaměřit na specifické produkty peroxidace lipidů, tzv. lipofuscinoidní pigmenty (LFP), v erytrocytech. Na základě fluorescenčních analýz LFP je možné najít specifický produkt v krvi u ACH.
Alzheimer´s disease (AD) is a serious neurodegenerative disorder accompanied by oxidative stress. Products of free radical reactions diffuse from primary sites and can be detected in cerebrospinal fluid (CSF) and blood. Such products represent potential biochemical markers for diagnosis of AD. Most studies are focused on CSF since its composition reflects pathological changes in the brain in AD. Increased levels of lipid and protein oxidative products have been found in CSF. Levels of vitamins were reduced in CSF. However, there are studies which show no difference between AD and controls. There is research on free radical products in blood in AD but results are not consistent. Several studies show increased oxidative products and reduced antioxidant in plasma. Nevertheless, others did not confirm it. Considering the investigation of a diagnostic biomarker for AD, specific end-products of lipid peroxidation, so called lipofuscin-like pigments (LFP), in erythrocytes represent an important possibility. A specific product in blood in AD can be found by means of fluorescence analyses of LFP.
- Klíčová slova
- biomarkery,
- MeSH
- Alzheimerova nemoc patofyziologie MeSH
- biologické markery krev MeSH
- financování organizované MeSH
- isoprostany diagnostické užití krev MeSH
- kyselina askorbová diagnostické užití krev MeSH
- malondialdehyd diagnostické užití krev MeSH
- oxidační stres MeSH
- peroxidace lipidů MeSH
- produkty pokročilé glykace diagnostické užití MeSH
- vitamin E diagnostické užití krev MeSH
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% O(2)) 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% CO(2)) 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 CO(2) with free radical processes. Copyright (c) 2008 John Wiley & Sons, Ltd.
- MeSH
- časové faktory MeSH
- cytoprotekce MeSH
- erytrocytární membrána metabolismus MeSH
- erytrocyty cytologie metabolismus MeSH
- fluorescenční spektrometrie MeSH
- hyperkapnie metabolismus MeSH
- hypoxie metabolismus MeSH
- krysa rodu rattus MeSH
- lipofuscin biosyntéza MeSH
- luminiscence MeSH
- luminol metabolismus MeSH
- malondialdehyd metabolismus MeSH
- peroxidace lipidů MeSH
- potkani Wistar MeSH
- volné radikály metabolismus MeSH
- železo metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- Alzheimerova nemoc patofyziologie MeSH
- peroxidace lipidů genetika MeSH
- psi MeSH
- volné radikály metabolismus MeSH
- zvířata MeSH
- Check Tag
- psi MeSH
- zvířata MeSH
- Publikační typ
- kongresy MeSH
