Is type 2 diabetes an early stage of Alzheimer's disease?
Based on the recently obtained data, scientists have concluded that the diagnosis of "type 2 diabetes mellitus" may mean that a person is already on the way to Alzheimer's disease. However, there is good news: diabetes-associated memory disorders can be cured, at least in rats.
According to associate professor from the State University of New York Ewan McNay, it is possible that drugs for the treatment of Alzheimer's disease can be used to prevent the development of cognitive function disorders at the stage of diabetes mellitus.
Alzheimer's disease cost the United States about $130 billion in 2011 alone. One of the main risk factors for the development of this disease is the presence of a history of type 2 diabetes mellitus. In this type of diabetes, liver cells, as well as muscle and adipose tissue, cease to respond properly to an increase in the concentration of insulin in the blood – a hormone that signals to cells about the need to absorb glucose contained in the blood. As a rule, the cause of the development of this disease is the use of excessive amounts of carbohydrate and fat-rich foods, causing sharp jumps in the level of insulin in the blood, which leads to a decrease in the sensitivity of cells to this hormone. In addition to the development of obesity, insulin resistance can lead to cognitive impairment, such as memory loss and confusion.
In 2005, researchers at Brown University, Rhode Island, working under the leadership of Susanne de la Monte, established a mechanism linking type 2 diabetes with an increased risk of developing Alzheimer's disease. It turned out that with this type of dementia, the hippocampus, a region of the brain involved in learning and memorization, loses sensitivity to insulin.
Keeping animals on a diet that causes the development of type 2 diabetes leads to the appearance of insoluble aggregates of beta-amyloid protein in their brains, which are considered the "calling card" of Alzheimer's disease. In addition, it has long been known that insulin plays a key role in memory processes. A comparison of these facts indicates that Alzheimer's disease is essentially a kind of diabetes of the brain.
Despite the fact that experts have not yet come to an unambiguous consensus on the causes of Alzheimer's disease, it is well known that this disease is accompanied by the formation of beta-amyloid plaques in the brain. Recently, more and more evidence has been received by the hypothesis that the cause of the symptoms of Alzheimer's disease is not the plaques themselves, but their precursors – small soluble aggregates of beta-amyloid, known as oligomers. Perhaps the appearance of insoluble plaques is the result of attempts by the body to isolate toxic oligomers.
In order to study the potential role of beta-amyloid in the development of cognitive impairment in type 2 diabetes, researchers working under the leadership of Evan McNay kept 20 rats on a fat-rich feed in order for them to develop type 2 diabetes. After that, in these animals, as well as in 20 healthy rats of the control group, an association of a dark cell with an electric shock was formed. Upon subsequent entry into the dark cage, the animals froze with fear. Measuring the duration of the period of immobility of animals is a standard test for assessing the state of their memory.
As expected, the memory of mice with diabetes mellitus was worse than that of healthy animals, which was manifested by twice as short periods of immobility in the dark. To clarify the underlying mechanisms of this phenomenon, the authors synthesized fragments of antibodies specific to beta-amyloid, which is part of insoluble plaques, and its soluble precursor molecules.
The introduction of antibodies specific to beta-amyloid insoluble plaques into the hippocampus of animals had no effect. At the same time, the introduction of antibodies specific to the soluble precursor returned the memory of the animals to normal.
Until now, it was believed that the extinction of cognitive function in type 2 diabetes mellitus is due to a violation of insulin-mediated signaling mechanisms. One of the consequences of this is a decrease in the ability of the hippocampus to transport energy in the form of glucose molecules to neurons in the process of performing a cognitive task. The accumulation of beta-amyloid plaques in animals and people with diabetes mellitus was considered an undesirable side effect of impaired insulin sensitivity.
However, the experimental results indicate that the real culprits are still beta-amyloid oligomers. Earlier work by other research groups has shown that insulin and beta-amyloid oligomers are cleaved by the same enzymes and that oligomers prevent insulin from interacting with its receptors in the hippocampus. Therefore, with an increased concentration of insulin in the body, which is typical for type 2 diabetes, enzymes break down mainly insulin. The remaining beta-amyloid oligomers accumulate in the form of aggregates that block the interaction of insulin and its specific receptors. The resulting vicious circle leads to a progressive disruption of the insulin-mediated signaling mechanism, accompanied by the extinction of cognitive function.
According to McNay, apparently, therapy with specific antibodies started the process of cleavage of beta-amyloid oligomers, which, in turn, made it possible for insulin to interact with its receptors. The accumulation of beta-amyloid in the brain is considered to be a consequence of events leading to impaired cognitive function in diabetes mellitus, however, apparently, everything happens exactly the opposite and the extinction of cognitive abilities associated with type 2 diabetes can be considered as an early stage of Alzheimer's disease.
The confirmation of this bold statement can lead to big changes. Given the fact that according to statistical estimates, the number of people with type 2 diabetes will grow from 382 million (currently) to 592 million by 2035, we can expect a similar surge in the incidence of Alzheimer's disease. If the formation of amyloid plaques can be stopped and the deteriorating cognitive functions restored at the stage of diabetes mellitus, it is possible that most of these patients will never develop Alzheimer's disease.
The next stage of the work is the reproduction of the results obtained. If successful, specialists will have to search for drugs that have the effects of antibodies used in experiments that would not need to be injected directly into the hippocampus. It will also be necessary to establish how much beta-amyloid can be eliminated from the brain without consequences, since in small concentrations this protein is necessary for memory formation.
Experts were very interested in the results obtained by McNay's group. However, they emphasize the need for further research, including studying the possible involvement of the effects of aging, since both type 2 diabetes and Alzheimer's disease are age-related diseases.
At the same time, McNay himself jokes that there is an alternative method of preventing type 2 diabetes and any subsequent Alzheimer's – going to the gym and reducing the consumption of sweets and fast food.
The results of the study were presented at the annual congress of the Society of Neuroscientists held on November 9-13 in San Francisco.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of New Scientist:
Jessica Griggs, Are Alzheimer's and diabetes the same disease?
03.12.2013