Patients with Alzheimer's Have Type 2 Diabetes, With Associated Increased Advanced Glycation End Products (AGEs) and Increased Expression of Receptor for AGEDs

 

Advanced glycation end products (AGEs) are lipid or protein materials that become highly glycated due to contact with sugars. They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney disease, and Alzheimer's disease

They play an important role in the development and aging of both healthy and unhealthy cells, as well as in the occurrence and progression of several degenerative diseases. These include cirrhosis of the liver, fatty liver, and multiple sclerosis. They also cause the destruction of the red blood cell (RBC), the formation of advanced glycation end products or AME (products of glycation) inside the red blood cells and the premature aging of tissues. Most of these proteins are unstable and changes their function when exposed to varying sugars. This process can be triggered by a number of environmental factors, including obesity, chronic alcohol abuse, hormonal changes, insulin resistance, tobacco use, anti-inflammatory drugs, medications used in the treatment of cancer, and environmental toxins.

In recent years, there have been a number of new studies that have examined the effect of advanced glycation end products on the human body. These studies have revealed that excessive accumulation of unprocessed proteins in cells may be a contributing factor in diabetes, obesity, cardiovascular disease, osteoporosis, rheumatoid arthritis, Alzheimer's disease, stroke, and many degenerative diseases. Some of these diseases are associated with increased concentrations of unprocessed sugars in the blood, as well as elevated blood pH levels. It has been proposed that the excessive levels of glucose within the cells may be produced via the glycation of proteins, which then contribute to the pathogenesis of most degenerative diseases.

Damage-associated molecular pattern interaction with their central receptor, receptor for advanced glycation end products, has found to increase the risk of Covid-19 in obese/diabetic patients. In November 2020, vTv Therapeutics Inc., a U.S.-based clinical-stage biopharmaceutical company, reported baseline characteristics for the enrolled subjects in the ongoing Elevage clinical study of azeliragon as a potential treatment for mild Alzheimer’s disease in people with type 2 diabetes. Approximately 35% of patients with Alzheimer’s disease have type 2 diabetes, with associated increased advanced glycation end products and increased expression of the Receptor for Advanced Glycation End products, the target for azeliragon.