The paradox of Alzheimer's disease sheds light on the mechanisms of memory loss
The human brain is constantly getting rid of irrelevant information, so we can rarely remember, for example, music we heard on the way to work, and other insignificant facts. Scientists at the Buck Institute, working under the leadership of Dr. Dale Bredesen, believe that the key factor in irreversible memory loss in Alzheimer's disease is hyperactivation of this normal mechanism of forgetting.
Last year, the authors managed to completely eliminate the possibility of developing Alzheimer's disease in genetically modified mice with a predisposition to the formation of amyloid plaques and protein deposits associated with Alzheimer's disease. To do this, they blocked a fragment of the amyloid precursor protein molecule (amyloid precursor protein, APP), in which it interacts with caspase enzymes that act as "molecular scissors". This prevented the splitting of the molecule into fragments. As a result, the animals retained normal memory and, despite the presence of a large number of beta-amyloid plaques in the brain, traditionally considered a sign of Alzheimer's disease, there were no signs of damage to nerve cells.
When studying human brain tissue, scientists have found that patients with Alzheimer's disease are characterized by a higher activity of the APP splitting process than people of the same age who do not suffer from this disease. At the same time, the study of brain tissue of healthy young people showed that the activity of APP splitting in them is 10 times higher than in old people with Alzheimer's disease. The authors believe that they know the explanation of this paradox.
The brain synthesizes beta-amyloid throughout life. The authors believe that it is involved in the regulation of synapses. According to Bredesen, the young brain functions very quickly, forming and erasing memories at a speed that far exceeds the speed of the less plastic brain of older people. The authors believe that Alzheimer's disease develops in the aging brain when a specific biochemical "switch" of the splitting process of the APP molecule gets stuck in the on position, which shifts the balance towards erasing memories.
The fact that beta-amyloid deposits are formed in the brain of many people without the development of any symptoms of Alzheimer's disease indicates that the critical link in the development of this disease is not the protein itself, but violations of the signaling mechanisms mediated by it. The researchers are confident that these disorders can be corrected with the help of therapeutic methods, and they are going to continue working on the mechanisms of regulation of the processes of preservation and erasure of memories.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily
21.03.2008