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Probing the Causes of Alzheimer’s
August 29, 2014   
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Researchers at the Nencki Institute of Experimental Biology in Warsaw are investigating molecular mechanisms responsible for the onset and development of various neurodegenerative diseases including Alzheimer’s.

The researchers say they are trying to establish methods for detecting biochemical signals marking the earliest stages of neurodegenerative diseases. Understanding the key factors responsible for neurodegeneration will in the future facilitate not only early detection of diseases but also preparation of effective treatments, say the researchers, who are pursuing their research at the Laboratory of High-Standard Preclinical Research at the Nencki Institute of Experimental Biology in Warsaw.

The Laboratory of High-Standard Preclinical Research is the newest of five recently-launched labs at the institute’s Neurobiology Center. It is ready to conduct preclinical tests for outside research institutions and firms. It has been outfitted with equipment including new-generation cell analyzers to facilitate research into the activity and safety of different compounds in cell lines including mice, rat and human neuronal cultures as well as in human blood cells and in animal and human cancer cell lines. In addition, the lab is adapted for conducting preclinical tests on mice models of neurodegenerative and immunodefective diseases.

During the next few years the researchers at the Laboratory of High-Standard Preclinical Research will primarily focus on Alzheimer's disease, which affects 3 percent of people aged 70 and over, 10 percent of people aged 80 and older, and half the entire population over 90 years of age.

“A longer life span leads to neurodegenerative diseases becoming a growing problem, not only for those affected by these diseases, but for society as a whole,” says Prof. Urszula Wojda from the Nencki Institute. “At present Alzheimer's disease is number three on the list of the most expensive diseases to treat, with global costs amounting to $600 billion annually. And we still do not have good methods for early diagnosis or fully effective therapies.”

In Alzheimer's disease, connections between synapses in the brain are damaged, which is accompanied by a gradual, long-term dying out of neurons. Progressive degeneration of neurons in the brain, especially in the hippocampus and cerebral cortex, results in memory and personality disorders and finally the decline of cognitive functions. It is likely that this disease starts even 20 years before the onset of the first symptoms and when the patient begins to notice them, often many neurons have already been lost.

Microscopic images of the brains of individuals with Alzheimer's disease show characteristic extracellular deposits of a protein known as beta amyloid. Furthermore, intracellular aggregates of tau protein have been observed in degenerated neurons. To date these changes, especially the formation and deposition of beta amyloid, have been treated as the possible main cause of the disease. Researchers around the world have been searching for a compound that effectively counteracts the amyloid. However, the newest drugs developed for this purpose show low effectiveness and serious side effects. It therefore seems more and more likely that these deposits and protein aggregates are the effect and not the cause of the disease.

In their search for the causes of Alzheimer's disease, the researchers are currently focusing on studying lymphocytes (cells of the immune system) collected from patients. One of their main objectives is to determine whether Alzheimer's disease is a systemic illness that involves distorted mechanisms of cell division. In this regard, changes within the brain would only constitute the most visible effect of a disease of the entire body. If this hypothesis is verified, lymphocytes could be used in early diagnosis and drug screening. Built at a cost of zl.52 million and opened in mid-November last year, the Neurobiology Center of the Nencki Institute is part of a major European project that aims to establish a Center for Preclinical Research and Technology (CePT) in Warsaw.

The Neurobiology Center houses five core facility laboratories: the Laboratory of Molecular Neurobiology, Laboratory of Tissue Structure and Function Imaging, Laboratory of Animal Models, Laboratory of Brain Imaging, and the Laboratory of High-Standard Preclinical Research. The laboratories are fitted with cutting-edge research equipment, including a magnetic resonance imaging (MRI) scanner.

In addition to conducting research, the Neurobiology Center aims to offer a friendly and attractive working environment for scientists from around the world specializing in areas such as neurobiology, biochemistry and molecular biology.

The Nencki Institute of Experimental Biology is run by the Polish Academy of Sciences. The institute was established in 1918 and is the largest non-university center for biological research in Poland. Priority fields for the institute include neurobiology, neurophysiology, cellular biology and biochemistry and molecular biology. There are 31 labs at the institute, among them a modern Laboratory of Confocal Microscopy, a Laboratory of Cytometry, and a Laboratory of Electron Microscopy, Behavioral and Electrophysiological Tests.

The CePT project, with a budget of over zl.388 million, is the biggest biomedical/biotechnology undertaking in Central and Eastern Europe. A system of core facility laboratories is being built in Warsaw’s Ochota district as part of the project. This system will integrate the research and development activities of many scientific institutions. The laboratories will make it possible to conduct basic and preclinical research meeting the highest European standards in areas such as protein functional and structural analyses, biomaterial physico-chemistry and nanotechnology, as well as medical technology, physiology and pathophysiology, oncology, neurobiology, genomics and research into age-related diseases.
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