The role of cholesterol in Alzheimer's disease – "acquired Down syndrome"
Researchers at the Linda Crnic Institute for Down Syndrome and the University of Colorado School of Medicine have found that the damaging effect of cholesterol on brain tissue and blood vessels is based on the same mechanism.
High cholesterol in the blood is associated with an increased risk of developing Alzheimer's disease and diseases of the cardiovascular system that are not directly related to the formation of atherosclerotic plaques, but so far the mechanisms triggered by it leading to the development of these pathologies have been unclear.
The results obtained by the authors indicate that cholesterol, especially in the form of low-density lipoproteins ("bad cholesterol"), disrupts the process of division of mouse and human cells. The result is an uneven distribution of doubled chromosomes between daughter cells and the accumulation of defective cells with an abnormal number of genes.
One of the important findings was the fact that, under the influence of cholesterol, cells with three copies of the chromosome (the 21st in human cells and the 16th in mouse cells) encoding beta-amyloid accumulated in brain tissue. This peptide is known for its key role in the formation of toxic aggregates deposited in the brain tissue of patients with Alzheimer's disease.
Trisomy on the 21st chromosome is an extremely important finding, as it is characteristic of all cells of patients with Down syndrome, which are characterized by brain pathologies, including the early development of dementia and Alzheimer's disease. The results of earlier studies showed that up to 10% of cells, including brain neurons, of patients with Alzheimer's disease have three copies of the 21st chromosome. Thus, Alzheimer's disease is a kind of acquired form of Down syndrome. Moreover, mutant genes underlying the development of hereditary forms of Alzheimer's disease lead to disturbances in the process of chromosome distribution, similar to those described by the authors for the effect of cholesterol.
The authors also revealed the presence of neurons with trisomy on chromosome 21 in the brain tissue of children with lipid histiocytosis (Niemann-Pick disease) type C. This hereditary neurodegenerative disease is caused by a mutation affecting cholesterol metabolism.
The identification of the problem caused by cholesterol will allow specialists to develop fundamentally new approaches to the treatment of many diseases characterized by violations of the process of cell division, including Alzheimer's disease, atherosclerosis and, possibly, cancer.
The authors have already found a simple potential method to prevent cholesterol-induced uneven distribution of chromosomes between daughter cells. They demonstrated that pretreatment of cell culture with ethanol prevents the effect of cholesterol on the division process – each daughter cell receives a full set of chromosomes. Unfortunately, at the level of the body, such prevention is most likely ineffective :)
The article Antoneta Granic & Huntington Potter Mitotic Spindle Defects and Chromosome Mis-Segregation Induced by LDL/Cholesterol—Implications for Niemann-Pick C1, Alzheimer's Disease, and Atherosclerosis is published in the journal PLOS ONE.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Colorado Denver: Cholesterol increases the risk of Alzheimer's and heart disease. http://www.ucdenver.edu/about/newsroom/newsreleases/Pages/Cholesterol-increases-risk-of-Alzheimers-and-heart-disease.aspx
19.04.2013