Dysfunction of Cerebral Endothelium in Alzheimer's disease

Alzheimer’s disease is the most common form of dementia in the elderly, which accounts up to 80 % of all cases. •Clinical manifestation of the disease includes cognitive impairments such as attention deficit, spatial disorientation, speech disorders, and progressive loss of memory. •In the late stage of Alzheimer's, people generally lose the ability to communicate coherently, experience a decline in physical abilities and require total assistance with personal care. •Those with Alzheimer's live an average of eight years after their symptoms become noticeable to others, but survival can range from four to 20 years, depending on age and other health conditions.-

Age-realted dementia in Kazahstan: adaptation of the 10/66 dementia research group population -based study protocol

Background. The prevalence of dementia is increasing worldwide as the population ages and affects 10 % of the population over 65 years old and 40 % of people over the age of 80.[1] In Kazakhstan, as well as in other countries around the world, the population of aged people has been increasing over the past decades. According to available statistics, by the end of 2013, the percentage of people aged 65 and older in Kazakhstan was 6.7% [2]. Given the fact that Kazakhstan's current population is about 17,221 million people [2], and based on data from the global statistics, it can be assumed that at least 115,000 elderly people could be suffering from age-related dementia. Nevertheless, such pathology is currently may not being diagnosed in Kazakhstan; consequently giving no accurate statistical data on the number of people suffering from this age-related pathology. Thus, the aim of this study is to estimate true prevalence of dementia and assess the risk factors associated with the disease

Impacts of membrane biophysics in Alzheimer’s disease: from amyloid precursor protein processing to Aβ peptide-induced membrane changes

An increasing amount of evidence supports the notion that cytotoxic effects of amyloid-β peptide (Aβ), the main constituent of senile plaques in Alzheimer’s disease (AD), are strongly associated with its ability to interact with membranes of neurons and other cerebral cells. Aβ is derived from amyloidogenic cleavage of amyloid precursor protein (AβPP) by β- and γ-secretase. In the nonamyloidogenic pathway, AβPP is cleaved by α-secretases. These two pathways compete with each other, and enhancing the non-amyloidogenic pathway has been suggested as a potential pharmacological approach for the treatment of AD. Since AβPP, α-, β-, and γ-secretases are membrane-associated proteins, AβPP processing and Aβ production can be affected by the membrane composition and properties. There is evidence that membrane composition and properties, in turn, play a critical role in Aβ cytotoxicity associated with its conformational changes and aggregation into oligomers and fibrils. Understanding themechanisms leading to changes in a membrane’s biophysical properties and how they affect AβPP processing and Aβ toxicity should prove to provide new therapeutic strategies for prevention and treatment of AD

Membrane biophysics and mechanics in Alzheimer's disease

Alzheimer's disease is a chronic neurodegenerative disorder characterized by neuronal loss, cerebrovascular inflammation, and accumulation of senile plaques in the brain parenchyma and cerebral blood vessels. Amyloid-β peptide (Aβ), a major component of senile plaques, has been shown to exert multiple toxic effects to neurons, astrocytes, glial cells, and brain endothelium. Oligomeric Aβ can disturb the structure and function of cell membranes and alter membrane mechanical properties, such as membrane fluidity and molecular order. Much of these effects are attributed to their capability to trigger oxidative stress and inflammation. In this review, we discuss the effects of Aβ on neuronal cells, astrocytes, and cerebral endothelial cells with special emphasis on cell membrane properties and cell functions

Differentiation of mesenchymal stem cells into hepatocytes

Acute and chronic liver diseases are common in Kazakhstan and other countries. These diseases are known to cause significant disability and death. In many cases, liver transplantation is the last resort for patients with end stage liver disease, but it is an extremely expensive procedure and is associated with many risks. The most important among them is an immune rejection. Autologous cell transplantation is a potential therapeutic approach for liver regeneration and could become an alternative to organ transplantation. In this regard, mesenchymal stem cells (MSCs) are a very attractive source for differentiation into hepatocytes. These cells can be isolated from bone marrow and adipose tissue of the patient and exponentially expanded in vitro. Transplantation of hepatocytes differentiated from MSCs could become a new promising approach in treatment of the patients with chronic liver conditions

Age-realted dementia in Kazahstan: adaptation of the 10/66 dementia research group population -based study protocol

Background. The prevalence of dementia is increasing worldwide as the population ages and affects 10 % of the population over 65 years old and 40 % of people over the age of 80.[1] In Kazakhstan, as well as in other countries around the world, the population of aged people has been increasing over the past decades. According to available statistics, by the end of 2013, the percentage of people aged 65 and older in Kazakhstan was 6.7% [2]. Given the fact that Kazakhstan's current population is about 17,221 million people [2], and based on data from the global statistics, it can be assumed that at least 115,000 elderly people could be suffering from age-related dementia. Nevertheless, such pathology is currently may not being diagnosed in Kazakhstan; consequently giving no accurate statistical data on the number of people suffering from this age-related pathology. Thus, the aim of this study is to estimate true prevalence of dementia and assess the risk factors associated with the disease

Isolation of primary human hepatocytes from cirrhotic liver

Chronic degenerative liver diseases are among most complex social, clinical and epidemiological health problems worldwide. This is due to the steady increase in the incidence and mortality of patients with this pathology. Orthotopic liver transplantation is the only way to save the lives of patients with decompensated diffuse and focal lesions of the liver. One-year survival after liver transplantation reaches 60-80%, but more than half of the patients on the waiting list do not survive until operation. In this regard, hepatocyte transplantation could be an option for the patients who are on the waiting list for organ transplantation

Isolation of primary human hepatocytes from cirrhotic liver

Chronic degenerative liver diseases are among most complex social, clinical and epidemiological health problems worldwide. This is due to the steady increase in the incidence and mortality of patients with this pathology. Orthotopic liver transplantation is the only way to save the lives of patients with decompensated diffuse and focal lesions of the liver. One-year survival after liver transplantation reaches 60-80%, but more than half of the patients on the waiting list do not survive until operation. In this regard, hepatocyte transplantation could be an option for the patients who are on the waiting list for organ transplantation

Impacts of Membrane Biophysics in Alzheimer's Disease: From Amyloid Precursor Protein Processing to Aβ Peptide-Induced Membrane Changes

An increasing amount of evidence supports the notion that cytotoxic effects of amyloid-β peptide (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD), are strongly associated with its ability to interact with membranes of neurons and other cerebral cells. Aβ is derived from amyloidogenic cleavage of amyloid precursor protein (AβPP) by β- and γ-secretase. In the nonamyloidogenic pathway, AβPP is cleaved by α-secretases. These two pathways compete with each other, and enhancing the non-amyloidogenic pathway has been suggested as a potential pharmacological approach for the treatment of AD. Since AβPP, α-, β-, and γ-secretases are membrane-associated proteins, AβPP processing and Aβ production can be affected by the membrane composition and properties. There is evidence that membrane composition and properties, in turn, play a critical role in Aβ cytotoxicity associated with its conformational changes and aggregation into oligomers and fibrils. Understanding the mechanisms leading to changes in a membrane's biophysical properties and how they affect AβPP processing and Aβ toxicity should prove to provide new therapeutic strategies for prevention and treatment of AD

Membrane biophysics and mechanics in Alzheimer's disease

Alzheimer's disease is a chronic neurodegenerative disorder characterized by neuronal loss, cerebrovascular inflammation, and accumulation of senile plaques in the brain parenchyma and cerebral blood vessels. Amyloid-β peptide (Aβ), a major component of senile plaques, has been shown to exert multiple toxic effects to neurons, astrocytes, glial cells, and brain endothelium. Oligomeric Aβ can disturb the structure and function of cell membranes and alter membrane mechanical properties, such as membrane fluidity and molecular order. Much of these effects are attributed to their capability to trigger oxidative stress and inflammation. In this review, we discuss the effects of Aβ on neuronal cells, astrocytes, and cerebral endothelial cells with special emphasis on cell membrane properties and cell functions