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.
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