Published: 2010-01-15 years Updated: 2010-07-11
Author: South Florida Medical College
Peer-reviewed publications: N / A
Move in: Main announcement | Publications
Summary: Down syndrome, cardiovascular disease, and diabetes appear to share the same pathogenesis as Alzheimers disease. Nearly 20 years ago, Huntington Potter caused a storm of controversy with the idea that Down syndrome and Alzheimer’s were the same disease. Now the proof is: He was right.
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Main announcement
Nearly 20 years ago, Huntington Potter caused a storm of controversy with the idea that Down syndrome and Alzheimer’s were the same disease. Now the proof is: He was right.
And that’s not all. Down syndrome, an artery-clogging cardiovascular disease and possibly even diabetes, appears to share a common pathogenesis with Alzheimer’s disease, Dr. Potter and colleagues at the Florida Alzheimer’s Disease Research Center, Institute of USF Health Byrd’s Alzheimer’s Disease, recently reported.
Two papers by the researchers – one in Molecular Biology of Cells and one in PLoS ONE – concern the Alzheimer’s disease-associated beta amyloid protein (amyloid protein), which damages the microtubule transport system responsible for Alzheimer’s disease. responsible for moving chromosomes, proteins, and other cargoes around inside cells. Both studies were conducted in mice and humans, in cell cultures that modeled Alzheimer’s disease. Together, the laboratory discoveries suggest that protecting this microtubule network from amyloid damage could be an effective way to prevent or even reverse Alzheimer’s disease and related disorders.
The first paper by Antoneta Granic and colleagues, published online December 23 in the journal Molecular Biology of the Cell, lays out the mechanism behind earlier work by Dr. Potter’s lab showing that All patients with Alzheimer’s disease contain some cells with three copies of chromosome 21, called trisomy 21, instead of the usual two. Trisomy 21 is a common feature of all cells in people with Down syndrome, a birth defect. Previous research has demonstrated that Alzheimer’s disease can be considered a late-onset form of Down syndrome.
Between the ages of 30 and 40, all people with Down syndrome develop Alzheimer’s-like encephalopathy, which includes the accumulation of nerve-dead clumps of sticky amyloid protein. This contributes to accelerated nerve cell loss and dementia.
With research reported on MBC, Dr. Potter and his colleagues have shown that the amyloid protein involved in Alzheimer’s disease is the culprit that interferes with the microtubule transport system inside the cell. The microtubules are responsible for separating the new chromosomes that duplicate when the cell divides. “Beta amyloid essentially creates potholes on protein highways that move cargo, including chromosomes, around the inside of cells,” said Dr Potter, who holds the Eric Pfeiffer Endowed Chair for Research Alzheimer’s disease, said.
When the microtubule network is disrupted, chromosomes can be transported incorrectly as the cell divides and, as a result, produces new cells with the wrong number of chromosomes and an abnormal gene. For example, Down syndrome cells contain three copies of the beta amyloid gene on chromosome 21 – leading to more accumulation of the “bad” amyloid protein throughout life, Dr. “Alzheimer’s disease is probably due in part to the continued growth of new trisomy 21 neurons, which amplify the disease process by producing additional beta amyloid.”
A second paper by lead author Jose Abisambra and colleagues, published December 31 in the online journal PLoS ONE, describes another consequence of the damaged microtubule network caused by amyloid proteins.
Many patients with Alzheimer’s disease also often develop vascular diseases and diabetes. Whether this coincidence is bad luck or due to a shared disease process is hotly debated. Research groups have investigated the role that low-density lipoprotein (LDL), the bad cholesterol that causes atherosclerosis, cardiovascular disease and stroke, may trigger the development of Alzheimer’s disease with mixed results. . However, the USF team focused on the potential impact of amyloid proteins on LDL metabolism. The receptor required to detect and utilize LDL is among the proteins transported by microtubules.
As their colleagues previously reported in the MBC paper, the second USF group found that the amyloid protein causes damage to the microtubule network. As a result, the receptor needed to pull LDL circulating in the blood into the body’s cells has trouble reaching the cell surface to pick up this bad cholesterol. This interference with LDL metabolism can allow bad cholesterol to build up in plaques that block blood supply to the brain and heart in people with Alzheimer’s disease, Dr.
Similarly, other important proteins – including insulin receptors and receptors for brain signaling molecules – are also capable of being locked inside cells when the transport system is damaged by amyloid or other factors. other. Dr Potter said: “Insulin receptors are needed to get blood sugar inside cells, where it can be used for energy. “So if these receptors can’t function properly, it can lead to diabetes and learning and memory problems.”
“We are beginning to understand how conditions such as cardiovascular disease and diabetes may represent some of the same underlying disease processes as Alzheimer’s disease, rather than as independent diseases that develop at the same time,” he said. patient”.
The studies were supported by funds from the USF Health Byrd Alzheimer Institute, Eric Pfeiffer Chair of Alzheimer’s Research, and the National Institute on Aging, a statewide Florida Center for Alzheimer’s Research funding at Southern University. Florida.
Articles cited:
1. “Alzheimer Ab Peptide Induces Chromosomal Misalignment and Heterozygism, Including Trisomy 21; Requirement for Tau and APP,” Antoneta Granic, Jaya Padmanabhan, Michelle Norden and Huntington Potter. Molecular biology of cells, December 23, 2009.
2. “Altered LDLR expression and localization in mouse and human cell culture models of Alzheimer’s disease”, Jose Abisambra, Tina Fiorella, Jaya Padmanabhan, Peter Neame, Inge Wefes and Huntington Potter, PLoS ONE, Vol. 5, No. 1. (January 2010).
USF Healt
USF Health (www.health.usf.edu) is dedicated to creating a health care model based on an understanding of whole health. It includes the University of South Florida colleges of medicine, nursing, and public health; schools of biomedical sciences as well as physiotherapy & rehabilitation sciences; and the USF Group of Physicians. With more than $380.4 million in research grants and contracts last year, the University of South Florida is one of the nation’s 63 top public research universities and one of 25 public research universities. nationally recognized institution of very high research activity designated as participatory by the community of the Carnegie Foundation for the Advancement of Teaching.
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