Analysis of Inflammatory processes in the human Entorhinal and Frontal cortex during normal aging and Alzheimer's disease


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Analysis of Inflammatory processes in the human Entorhinal and Frontal cortex during normal aging and Alzheimer's disease
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Université de Lausanne, Faculté de biologie et médecine
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Background: Alzheimer's disease (AD) is the most common cause of dementia in the world. This disease is characterized by neuronal degeneration as well as the accumulation of abnormal proteins. An increase of evidences shows that the disease is also accompanied by a reactive gliosis, which allows advancing the hypothesis that an inflammatory process occurs in the brain through an increase in microglia and astrocytes density. These cells respond dynamically to neurodegenerative lesions inducing a local activation of immune components and acquiring the ability to secrete pro-inflammatory cytokines such as IL-1β and TNF-α thereby triggering an immune cascade. It is assumed that chronic inflammatory processes in specific areas of the brain such as the entorhinal and frontal cortex could contribute to the worsening of the clinical symptoms of the disease. Moreover, some studies have suggested that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may help to curb or even prevent AD.
Method: In order to understand the relationship between inflammatory processes and Alzheimer's disease, the inflammatory changes were investigated in human brain tissues of the entorhinal and the frontal cortex from control and AD subjects by using one-dimensional electrophoresis and immunostaining combined with chemiluminescence. A polyclonal GFAP antibody was used to detect the reactive astrogliosis, a monoclonal AD2 antibody to evaluate the accumulation of pathological tau protein and a monoclonal β-amyloid antibody, which reacts with the component of senile plaques. Three antibodies were used to detect specific inflammatory proteins, a monoclonal TNF-α antibody, a monoclonal IL-1β antibody and a monoclonal NF-κB antibody. Quantitative and statistical analyses were then performed to compare the respective concentrations of these proteins in the two brain regions between a control group and moderate and severe Alzheimer's disease cases.
Results: The results highlighted a disparity in the pathological accumulation of tau and β- amyloid proteins not only according to the stage of the disease but also depending on the brain region. It also appears that the reactive astrogliosis and the inflammatory processes, found in significant quantities at the beginning of AD, do not persist indefinitely and that there is a decrease of these proteins when the disease reaches an advanced stage.
Conclusions: Alzheimer's disease is marked by the presence of a significant amount of glial cells as well as a high density of inflammatory molecules. However, these components are involved early in the development of the disease and do not seem to be correlated with the worsening of the cognitive decline. Therapies focused on inflammatory processes, as for example NSAIDs, should then be administered as soon as possible when the symptoms are still mild or even not yet clinically diagnosed. New diagnostic techniques are therefore necessary to detect the disease in the very early stages and the development of targeted treatments remains one of the major challenges of current research about Alzheimer's disease.
Alzheimer's disease, neuroinflammation, astrocytes, microglia
Création de la notice
03/09/2015 10:07
Dernière modification de la notice
20/08/2019 14:55
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