Metabolic Abnormalities of Erythrocytes as a Risk Factor for Alzheimer's Disease.

Alzheimer's disease (AD) is a slowly progressive, neurodegenerative disorder of uncertain etiology. According to the amyloid cascade hypothesis, accumulation of non-soluble amyloid β peptides (Aβ) in the Central Nervous System (CNS) is the primary cause initiating a pathogenic cascade leading to the complex multilayered pathology and clinical manifestation of the disease. It is, therefore, not surprising that the search for mechanisms underlying cognitive changes observed in AD has focused exclusively on the brain and Aβ-inducing synaptic and dendritic loss, oxidative stress, and neuronal death.

Portacaval shunting causes differential mitochondrial superoxide production in brain regions.

The portacaval shunting (PCS) prevents portal hypertension and recurrent bleeding of esophageal varices. On the other hand, it can induce chronic hyperammonemia and is considered to be the best model of mild hepatic encephalopathy (HE). Pathogenic mechanisms of HE and dysfunction of the brain in hyperammonemia are not fully elucidated, but it was originally suggested that the pathogenetic defect causes destruction of antioxidant defense which leads to an increase in the production of reactive oxygen species (ROS) and the occurrence of oxidative stress.

Relationship between chronic disturbance of 2,3-diphosphoglycerate metabolism in erythrocytes and Alzheimer disease.

Alzheimer disease (AD) is one of the most common neurodegenerative disorders widely occurring among the elderly. The pathogenic mechanisms involved in the development of this disease are still unknown. In AD, in addition to brain, a number of peripheral tissues and cells are affected, including erythrocytes.

Critical analysis of Alzheimer's amyloid-beta toxicity to mitochondria.

Amyloid-beta peptide (Abeta) is believed to be a central player in the Alzheimer disease (AD) pathogenesis. However, its mechanisms of toxicity to the central nervous system are unknown. To explore this area, investigators have recently focused on Abeta-induced cellular dysfunction.

Differential up-regulation of ammonia detoxifying enzymes in cerebral cortex, cerebellum, hippocampus, striatum and liver in hyperammonemia.

In order to gain insight into the ammonia-detoxification mechanisms in the brain and liver tissues, we have investigated the effects of hyperammonemia in rats, in vivo, on the activity levels of a number of ammonia- and glutamate-metabolizing enzymes in mitochondria and the cytosolic fractions of the cerebral cortex, cerebellum, hippocampus, striatum and liver. In general, the ammonia metabolizing enzymes - glutaminase, glutamine synthetase, glutamate dehydrogenase, AMP deaminase, adenosine deaminase, as well as aspartate aminotransferase and alanine aminotransferase - are differentially upregulated in various brain and liver regions of the hyperammonemic rats, indicating that divergent ammonia-detoxification mechanisms are involved in the various brain regions and liver in acute hyperammonemia.

Impact of amyloid β25-35 on membrane stability, energy metabolism, and antioxidant enzymes in erythrocytes.

Amyloid β25-35 (Aβ25-35) represents a neurotoxic fragment of Aβ1-40 or Aβ1-42, and is implicated in the progressive neurodegeneration in cases of the Alzheimer disease (AD). Amyloid β25-35 was shown to lyse rat erythrocytes (RBCs) of all ages, and the extent of the RBC toxicity is directly correlated with Aβ25-35 concentration and cell age. Activities of glycolytic, antioxidant, and Na(+)/K(+)-adenosine triphosphatase (ATPase) enzymes, in vivo, are significantly decreased in older RBCs as compared to the young RBCs.

Age-related defects in erythrocyte 2,3-diphosphoglycerate metabolism in dementia.

Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in the brain with aging contribute to the pathogenesis of AD. These changes can be found systematically and thus can be used as potential biomarkers.

Implication of the nutritional and nonnutritional factors in the context of preservation of cognitive performance in patients with dementia/depression and Alzheimer disease.

It has been postulated that Alzheimer disease (AD) is a systemic process, which involves multiple pathophysiological factors. A combination of pharmacotherapy and nonpharmacological interventions has been proposed to treat AD and other dementia. The nonpharmacological interventions include but are not limited to increasing sensory input through physical and mental activities, in order to modify cerebral blood flow and implementing nutritional interventions such as diet modification and vitamins and nutraceuticals therapy to vitalize brain functioning.

Pathogenesis of Alzheimer disease: role of oxidative stress, amyloid-β peptides, systemic ammonia and erythrocyte energy metabolism.

Aβ exerts prooxidant or antioxidant effects based on the metal ion concentrations that it sequesters from the cytosol; at low metal ion concentrations, it is an antioxidant, whereas at relatively higher concentration it is a prooxidant. Thus Alzheimer disease (AD) treatment strategies based solely on the amyloid-β clearance should be re-examined in light of the vast accumulating evidence that increased oxidative stress in the human brains is the key causative factor for AD. Accumulating evidence indicates that the reduced brain glucose availability and brain hypoxia, due to the relatively lower concentration of ATP and 2,3-diphosphoglycerate, may be associated with increased concentration of endogenous ammonia, a potential neurotoxin in the AD brains.

Antioxidant status and energy state of erythrocytes in Alzheimer dementia: probing for markers.

Subject age and brain oxidative stress play pivotal roles in Alzheimer disease (AD) pathology. Erythrocytes (red blood cells: RBC) are considered as passive "reporter cells" for the oxidative status of the whole organism, not active participants in mechanisms of AD pathogenesis and are not well studied in AD. The aim of this work is to assess whether the antioxidant status and energy state of RBC from elderly people change in AD.

Subcellular and metabolic examination of amyloid-beta peptides in Alzheimer disease pathogenesis: evidence for Abeta(25-35).

Amyloid-beta peptide (Abeta) is a central player in the pathogenesis and diagnosis of Alzheimer disease. It aggregates to form the core of Alzheimer disease-associated plaques found in coordination with tau deposits in diseased individuals. Despite this clinical relevance, no single hypothesis satisfies and explicates the role of Abeta in toxicity and progression of the disease.

Encapsulation of glutamine synthetase in mouse erythrocytes: a new procedure for ammonia detoxification.

There are a number of pathological situations in which ammonia levels increase leading to hyperammonemia, which may cause neurological alterations and can lead to coma and death. Currently, there are no efficient treatments allowing rapid and sustained decrease of ammonia levels in these situations. A way to increase ammonia detoxification would be to increase its incorporation in glutamine by glutamine synthetase.

Effects of amyloid-beta peptides on hydrogen peroxide-metabolizing enzymes in rat brain in vivo.

Amyloid-beta (Abeta) peptides are components of senile plaques initiating degeneration of brain neurons in Alzheimer's disease. They increase reactive oxygen species generation that may exceed the defensive capacity of cells. To test the hypothesis, this study investigated the in vivo effects of Abeta peptides on mitochondrial and non-mitochondrial enzymic sources of reactive oxygen species and antioxidant enzymes in rat brain.