Dementia Differences in Alzheimer's Proteins

Dementia: differences discovered in Alzheimer's proteins

07/02/2014

The course of Alzheimer's disease, in which sufferers suffer from a deficiency of the memory and orientation function of the brain, sometimes vary enormously. The treatments are often disappointing. Researchers have now gained new insights into the disease and discovered that there are several strains of abnormally altered proteins.

Different course of disease in Alzheimer's patients
Alzheimer's disease is a dramatic fate for those affected. The neurodegenerative disease can not be cured. But researchers have now found a possible explanation for why Alzheimer's disease in patients is different and the development of drugs is so difficult. Like a team around Stanley Prusiner of the University of California in San Francisco in the magazine „Proceedings of the National Academy of Sciences“ („PNAS“), there are at least two different strains of pathologically altered proteins, so-called prions. The biochemist and physician Prusiner received the 1997 Nobel Prize in Medicine for the discovery of prions.

Findings may help in the development of new drugs
„Our findings could help delineate Alzheimer's disease at the molecular level and develop drugs against beta-amyloid prions“, write the scientists. Beta-amyloid is a protein that occurs during normal metabolism but is usually broken down. But pathologically altered beta-amyloids accumulate in large quantities in the brain and gradually destroy nerve cells. As the researchers emphasized, they have a contagious effect and so pathological changes can be transferred to healthy beta-amyloids.

Experiments with genetically modified mice
The scientists created artificial beta-amyloids consisting of 40 or 42 amino acids to analyze the disease processes. They injected them into the brains of genetically modified mice that are susceptible to the human form of Alzheimer's disease, and indeed different deposits developed: those of beta-amyloid-40 had long fibers, those of beta-amyloid-42 had short fibers. In a second experiment, the physicians tested brain samples from several patients who had died of various hereditary variants of Alzheimer's disease, the so-called Arctic mutation and the Swedish mutation. They then injected the solutes into the brains of the genetically engineered mice. The mice also developed different appearances of the disease. The scientists showed these differences with biochemical reactions as well as imaging techniques.

Often disappointing treatment results
The team around Prusiner also injected mice with brain tissue from two patients who had non-hereditary Alzheimer's disease. In one case the animals showed the same clinical picture as the Swedish mutation and in the other case a mixture of Arctic and Swedish mutations. For the researchers, the enrichment of a beta-amyloid form with only 38 amino acids was a clear hallmark of the Arctic mutation. The authors write that these differences between beta-amyloid variants may also explain the often disappointing results in the treatment of Alzheimer's patients with monoclonal antibodies: „Although these antibodies may have been administered too late in the course of disease to improve, differences in beta-amyloid strains in Alzheimer's patients may also have contributed to the failure.“

Alzheimer's is the most common of dementias
In Germany, according to the German Society for Psychiatry and Psychotherapy, Psychosomatics and Neurology about 1.4 million people are affected by dementia. Alzheimer's is the most common dementia disease. Experts predict that patient numbers will double by 2050. At the present medical level, a cure of the disease is not possible, only a delay in the course of the disease and a relief of the symptoms can be achieved. It may be that the new findings can help to develop new treatment approaches. (Ad)