Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Studies demonstrate link among Alzheimer's disease, Down syndrome and atherosclerosis

18.01.2010
Studies implicate damage inflicted by amyloid protein as shared disease mechanism

Nearly 20 years ago Huntington Potter kicked up a storm of controversy with the idea that Down syndrome and Alzheimer’s were the same disease. Now the evidence is in: He was right.

And that’s not all. Down syndrome, artery-clogging cardiovascular disease, and possibly even diabetes, appear to share a common disease mechanism with Alzheimer’s disease, Dr. Potter and colleagues at the Florida Alzheimer’s Disease Research Center, USF Health Byrd Alzheimer’s Institute, recently reported.

The researchers’ two papers – one in Molecular Biology of the Cell and the other in PLoS ONE -- implicate the Alzheimer’s-associated protein beta amyloid (amyloid protein), which damages the microtubule transport system responsible for moving chromosomes, proteins and other cargo around inside cells. Both studies were done in mice and humans cell cultures modeling Alzheimer’s disease. Together, the laboratory discoveries suggest that protecting the microtubule network from this amyloid damage might be an effective way to prevent or even reverse Alzheimer’s disease and associated disorders.

The first paper, by Antoneta Granic and colleagues published online Dec. 23 in Molecular Biology of the Cell, provides the mechanism behind previous work by Dr. Potter’s laboratory showing that all Alzheimer’s disease 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. This earlier work demonstrated that Alzheimer’s disease could be considered a late onset form of Down syndrome.

By age 30 to 40, all people with Down syndrome develop the same brain pathology seen in Alzheimer’s disease, including a nerve-killing buildup of sticky amyloid protein clumps. This contributes to accelerated nerve cell loss and dementia.

With the study reported in MBC, Dr. Potter and his colleagues now show 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 the protein highways that move cargo, including chromosomes, around inside cells,” said Dr. Potter, who holds the Eric Pfeiffer Endowed Chair for Research on Alzheimer’s Disease.

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 says. “Alzheimer’s disease probably is caused in part from the continuous development of new trisomy 21 nerve cells, which amplify the disease process by producing extra beta amyloid.”

The second paper by lead author Jose Abisambra and colleagues, published Dec. 31 in the online journal PLoS ONE, describes another consequence of the damaged microtubule network caused by the amyloid protein.

Many Alzheimer’s disease patients also commonly develop vascular diseases and diabetes. Whether this coincidence is bad luck or due to shared disease processes is intensely debated. Research teams 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, the USF group focused on the amyloid protein’s potential effects on LDL metabolism. The receptor needed to detect and use LDL is among the proteins transported by the microtubules.

As previously reported by their colleagues in the MBC paper, the second 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 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,” Dr. Potter said. “So, if these receptors are unable to function properly, it may lead to diabetes and problems with learning and memory.”

“We’re beginning to understand how conditions like cardiovascular disease and diabetes may manifest some of the same underlying disease processes as Alzheimer’s disease,” he said, “rather than being independent diseases that just happen to develop in the same patient.”

The studies were supported by funds from the USF Health Byrd Alzheimer’s Institute, the Eric Pfeiffer Chair for Research on Alzheimer’s Disease, and the National Institute on Aging, sponsor of the statewide Florida Alzheimer’s Disease Research Center at the University of South Florida.

Journal articles cited:

1. “Alzheimer Ab Peptide Induces Chromosome Mis-segregation and Aneuploidy, including Trisomy 21; Requirement for Tau and APP,” Antoneta Granic, Jaya Padmanabhan, Michelle Norden, and Huntington Potter. Molecular Biology of the Cell, Dec. 23, 2009.

2. “LDLR Expression and Localization Are Altered 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, Volume 5, Issue 1. (January 2010).

- USF Health –
USF Health (www.health.usf.edu) is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $380.4 million in research grants and contracts last year, the University of South Florida is one of the nation’s top 63 public research universities and one of only 25 public research universities nationwide with very high research activity that is designated as community-engaged by the Carnegie Foundation for the Advancement of Teaching.

Anne DeLotto Baier | EurekAlert!
Further information:
http://www.usf.edu

More articles from Studies and Analyses:

nachricht New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Disarray in the brain
18.12.2017 | Universität zu Lübeck

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Optical Nanoscope Allows Imaging of Quantum Dots

Physicists have developed a technique based on optical microscopy that can be used to create images of atoms on the nanoscale. In particular, the new method allows the imaging of quantum dots in a semiconductor chip. Together with colleagues from the University of Bochum, scientists from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute reported the findings in the journal Nature Photonics.

Microscopes allow us to see structures that are otherwise invisible to the human eye. However, conventional optical microscopes cannot be used to image...

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Rutgers scientists discover 'Legos of life'

23.01.2018 | Life Sciences

Seabed mining could destroy ecosystems

23.01.2018 | Earth Sciences

Transportable laser

23.01.2018 | Physics and Astronomy

VideoLinks Science & Research
Overview of more VideoLinks >>>