by Few diseases have as devastating an impact as Alzheimer’s. Although we are aware that with age we lose memory, we are terrified by the idea that we will eventually not be able to recognize our loved ones or ourselves. Those memories, which have been stored in the brain for years, fade until they disappear. Although efforts to find a treatment have not yet yielded the desired results, we have learned a lot along the way.
Recent research has proposed a new approach to the development of Alzheimer’s disease. This might not just be a question of the buildup of beta-amyloid plaques and hyperphosphorylated tau tangles, as previously thought, but also of how our brain cells interact with insulin.
Insulin is a hormone that regulates blood glucose concentrations, which is why it is closely linked to another disease, diabetes mellitus. In fact, both diseases share risk factors: advanced age, diet, obesity and chronic inflammation.
Could there be a relationship between the brain and the pancreas that links the two diseases?
Let’s imagine for a moment that neural connections resemble cables in an electrical network through which thought and memory information would be transmitted. These cables start from neurons and reach others. Neurons are cells that need fuel to function, and the essential fuel is, precisely, glucose. Insulin acts like a bell on the door of cells. When that bell rings, the cell knows to open the door for glucose to enter. Without that bell, even if there is abundant glucose in the blood, the cell does not notice, it does not open the door and it does not receive the fuel.
When the cell receives more glucose than it needs, it ends up generating insulin resistance. That is, he becomes reluctant to open the door. That is why insulin resistance, linked to future type 2 diabetes, promotes the accumulation of sugar in the blood. Besides, It promotes the formation of beta-amyloid plaques, characteristics of Alzheimer’s.
Studies with rats have revealed that the administration of streptozocin, a drug used to induce diabetes in animal models, generates both insulin resistance and neurodegeneration similar to that of Alzheimer’s. The relationship has also been observed in humans, although it has not been linked to a greater accumulation of beta-amyloid or tau tangles in brain autopsies.
The inflammation link
A chronic state of low-grade inflammation generated by insulin resistance would also link both diseases. Inflammation is a fundamental process to combat external aggressions and repair the damage caused. When it becomes chronic, it can lead to alterations that are associated with metabolic diseases such as obesity, cardiovascular diseases, diabetes and Alzheimer’s.
In this scenario of insulin resistance, oxidative stress and inflammation, cells enter apoptosis (programmed cell death). If that happens, if the cells die, the network of cables becomes tangled and the brain does not function properly. Then the patient begins to forget and stops processing the information. Alzheimer’s appears.
All of this suggests that metabolic problems may be the key to both diseases.. For this reason, some researchers have suggested that Alzheimer’s be considered a new type of diabetes.
Type 3 diabetes?
The new type of diabetes would be called “type 3 diabetes.” It would join type 1, with a more genetic than environmental origin; type 2, with more environmental than genetic influence; and gestational, which occurs in some pregnant women. The term emerged in 2005 in the University of Rhode Islandwhose researchers proposed that Alzheimer’s could be a form of cerebral diabetes, characterized by insulin resistance and metabolic dysfunction.
Although it is important to note that this is not a term accepted by the entire scientific community, it is a hypothesis that can be useful to contribute to a more complete view of the disease.
The links between the two diseases are becoming stronger, but there is still much to discover, particularly about how to use this information for the benefit of patients. Given that the insulin resistance and inflammation play central roles, they could share therapeutic strategies. In that sense, promoting healthy lifestyles, including diet, could have a positive impact on the prevention and treatment of both diabetes and Alzheimer’s.
The connection between Alzheimer’s and diabetes can transform our understanding of both diseases. The idea of type 3 diabetes, although it does not have a scientific consensus, can open new doors to research that links the two diseases, with insulin resistance and inflammation at the center of the stage, as well as to effectiveness. With each new discovery we get a little closer to treating diseases that affect millions of people around the world. Are we on the threshold of a new era in Alzheimer’s research? Only time and science will be able to answer this question.
Article published in The conversation.
Javier Sánchez Perona
Senior Scientist of the CSIC and Associate Professor of the Pablo de Olavide University, Instituto de la Grasa (IG – CSIC)
