Scientists claim to have found a link among Alzheimer's, Down Syndrome, cardiovascular disease, and possibly even diabetes.
A team from the Florida Alzheimer's Disease Research Center and USF Health Byrd Alzheimer's Institute has based its findings on an analysis of two studies done in mice and humans cell cultures modelling Alzheimer's disease.
The first study, published in the 'Molecular Biology of the Cell' journal provides the mechanism behind previous work by Dr Huntington Potter showing that Alzheimer's patients harbor some cells with three copies of chromosome 21, known as trisomy 21, instead of the usual two.
Trisomy 21 is a characteristic shared by all the cells in people with the birth defect Down syndrome as well. Dr Potter and his colleagues have showed that the Alzheimer's-associated amyloid protein is the culprit that interferes with the microtubule transport system inside cells.
The microtubules are responsible for segregating newly duplicated chromosomes as cells divide. "Beta amyloid basically creates potholes in protein highways that move cargo, including chromosomes, around inside cells," said Dr Potter said.
When the microtubule network is disrupted, chromosomes can be incorrectly transported as cells divide and the result is new cells with the wrong number of chromosomes and an abnormal assortment of genes. 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 over a lifetime, Dr Potter said.
The second study, published in the 'PLoS One' journal, describes a consequence of the damaged microtubule network caused by the amyloid protein.
Many Alzheimer's disease patients also commonly develop vascular diseases and diabetes. The researchers have investigated the role that low-density lipoprotein (LDL), the bad cholesterol that causes atherosclerosis, cardiovascular disease and stroke, may play in the development of Alzheimer's with mixed results.
However, they focused on amyloid protein's potential effects on LDL metabolism. The receptor needed to detect and use LDL is among the proteins transported by the microtubules. The USF team found that the amyloid protein inflicts damage to the microtubule network. As a consequence, the receptor needed to pull LDL circulating throughout the bloodstream into the body's cells has trouble getting to the cell surface to retrieve this bad cholesterol.
"This interference with LDL metabolism may allow bad cholesterol to build up in into plaques that choke off blood supply to the brain and heart in people with Alzheimer's," Dr Potter said. Similarly, other key proteins – including insulin receptors and receptors for brain signaling molecules -- are also likely locked inside cells when the transport system is damaged by amyloid or other factors, the scientists said.
"The insulin receptors are needed to get blood sugar inside the cell where it can be used for energy. The nerve cell signaling receptors help promote memory and learning. So, if these receptors are unable to function properly it may lead to diabetes and memory problems," he said.