Down syndrome, Alzheimer's disease, atherosclerosis and diabetes: one cause, many consequences
The idea expressed about 20 years ago by Huntington Potter that Down syndrome and Alzheimer's disease are essentially the same disease caused a huge resonance in the scientific and medical community. Recently, Dr. Potter and his colleagues from the University of South Florida (Tampa) have received evidence of the validity of this assumption.
Moreover, they published the results of two papers indicating that the same mechanism underlies the development of Alzheimer's disease, Down syndrome, atherosclerosis and, possibly, even diabetes. The authors claim that the beta-amyloid protein associated with Alzheimer's disease, which damages the cell transport system consisting of microtubules, disrupts the movement of chromosomes, proteins and other molecules through the cell volume. Both studies were carried out on cultures of mouse and human cells with simulated symptoms of Alzheimer's disease. In general, laboratory data indicate that protecting microtubules from beta-amyloid-induced damage can not only prevent, but also cure Alzheimer's disease and associated diseases.
The first article, "Alzheimer Ab Peptide Induces Chromosome Mis-segregation and Aneuploidy, including Trisomy 21; Requirement for Tau and APP", published in the preliminary on-line version of the journal Molecular Biology of the Cell, explains the mechanism of the appearance in the brain of patients with Alzheimer's disease of a certain number of cells having three 21st chromosomes instead of two. This phenomenon, trisomy 21, is characteristic of all cells of people with congenital Down syndrome. The fact that such cells are present in the brains of all patients with Alzheimer's disease was identified by the staff of Dr. Potter's laboratory as part of earlier work and served as a prerequisite for the hypothesis that Alzheimer's disease can be considered an elderly Down syndrome.
At the age of 30-40 years, all patients with Down syndrome develop a brain pathology similar to that observed in Alzheimer's disease, one of the symptoms of which is the accumulation of beta-amyloid aggregates toxic to brain cells. This contributes to the progression of dementia and the rapid death of nerve cells.
The authors demonstrated that the cause of cell death is precisely beta-amyloid, which disrupts the functioning of the intracellular transport system consisting of microtubules. During cell division, this system secures the separation of newly formed copies of chromosomes.
Beta-amyloid violates the integrity of the protein walls of microtubules, which ensure the movement of various loads, including chromosomes, through the volume of the cell. As a result, cells with the wrong number of chromosomes or an abnormal set of genes may appear. For example, the cells of people with Down syndrome contain three copies of the 21st chromosome and, accordingly, three copies of the gene encoding beta-amyloid located on it, which leads to an accelerated accumulation of this protein in brain tissue. Perhaps one of the reasons for the development of Alzheimer's disease is the constant formation of new nerve cells with trisomy 21, actively producing amyloid-beta, which further aggravates the course of the disease.
The second article, "LDLR Expression and Localization Are Altered in Mouse and Human Cell Culture Models of Alzheimer's Disease", published on December 31 in the online version of the journal PLoS One, deals with another consequence of damage to the microtubule system caused by beta-amyloid.
Alzheimer's disease is often accompanied by blood vessel diseases and diabetes. Some experts are of the opinion that this fact is a mere coincidence, while others believe that there is some common cause of the development of these diseases. The study of the possible role that low-density lipoproteins (LDL, "bad cholesterol"), which cause atherosclerosis, cardiovascular diseases and stroke, can play in the development of Alzheimer's disease, has led scientists working on this issue to contradictory results. However, the authors decided to devote their work to studying the possible effect of beta-amyloid on the metabolism of low-density lipoproteins.
The receptor necessary for cells to recognize and utilize low-density lipoproteins, as well as many other proteins, moves inside the cell through the microtubule system. The researchers found that the disorders of the transport system caused by beta-amyloid lead to the fact that the receptor synthesized in the cytoplasm of the cell does not reach its membrane. As a result, the cell loses its ability to capture cholesterol circulating in the bloodstream, which is deposited on the walls of blood vessels in the form of plaques that disrupt the blood supply to the brain and heart of patients with Alzheimer's disease.
It is quite possible that a similar fate befalls other important proteins, including receptors for the hormone insulin responsible for glucose utilization and signaling molecules that ensure the interaction of brain cells. The result of this may be the development of diabetes and disorders of cognitive functions, including the processes of memorization.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru Based on ScienceDaily: Studies Demonstrate Link Among Alzheimer's Disease, Down Syndrome and Atherosclerosis.
19.01.2010