Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New way of controlling cholesterol may help treat Alzheimer’s

14.10.2004


A new approach to controlling blood cholesterol levels that is already being investigated to prevent cardiovascular disease also may be a potential treatment for Alzheimer’s disease. In their report in the October 14 issue of Neuron, researchers from Massachusetts General Hospital (MGH) show that blocking a pathway that controls the distribution of cholesterol in cells dramatically reduces the number of amyloid plaques in the brains of transgenic mice. Some of the treated mice were much better at learning their way through a maze than were untreated mice.



"We found that this way of reducing cholesterol levels in the brains of living animals both decreased amyloid deposition and improved learning," says the study leader Dora Kovacs, PhD, director of the Neurobiology of Disease Laboratory in the Genetics and Aging Research Unit of MassGeneral Institute for Neurodegenerative Disorders. "As far as we know, this is the first study of cholesterol metabolism’s impact on amyloid levels that included cognitive testing."

Researchers have been investigating a potential relationship between cholesterol metabolism and Alzheimer’s since it was found that a particular variant of the gene for a protein called apoE significantly increased risk of the disease. Since the apoE protein transports cholesterol, that discovery suggested that disruption of cholesterol handling might cause or worsen the development of the amyloid plaques that characterize Alzheimer’s disease. In addition, some epidemiologic studies have suggested that people taking statin drugs to control blood cholesterol have a reduced incidence of Alzheimer’s.


In 2001 Kovacs’ team showed in cells that the activity of an enzyme called ACAT, which controls whether cholesterol is stored in the cellular membrane or in intracellular droplets, also appears to regulate the formation of amyloid-beta, the protein fragments that make up amyloid plaques. The current study was designed to test that same approach in living animals.

At first, researchers tested whether the ACAT inhibitor used in the 2001 study would affect cholesterol storage in brain cells of mice. Because ACAT inhibitors are metabolized quickly, the researchers used implantable pellets that release the compound in a steady manner and found that the inhibitor significantly reduced the number of cholesterol droplets in brain cells of normal mice.

They then implanted inhibitor pellets in mice with a human gene that leads to amyloid plaque formation. Examination of brain tissue after two months of treatment found that mice receiving the ACAT inhibitor had 90 percent less plaque than did transgenic mice who received placebo pellets. The results were even more dramatic in female mice, who usually develop plaques earlier than males do. Biochemical analysis of mouse brain tissue showed that the inhibitor probably prevents amyloid-beta production, rather than reducing its deposition.

To evaluate the effect of ACAT inhibitor treatment on the mice’s cognitive abilities, the researchers had groups of treated and untreated mice swim through a water maze three times a day for four days. The inhibitor did not make a difference for the male mice, which was expected since only female mice would be expected to have enough amyloid in their brains to reduce their ability to find the hidden platform in the water. But those females who received the inhibitor were markedly better at learning the maze than were females with placebo pellets only. In fact, treated female mice learned the maze as well or better than nontransgenic mice did.

While the particular ACAT inhibitor used in this study is not yet appropriate for human trials, Kovacs notes, other ACAT inhibitors are in the process of clinical testing in humans for cardiovascular disease. Her group is now studying one that has been in Phase 3 clinical trials. "It’s possible that combining these inhibitors with statin drugs could have even more beneficial effects. If we can duplicate what we found in this animal study with the drug that reached Phase 3 human trials, we could cut ten years from the usual drug development timetable," she says.

Trying to reduce amyloid deposition through cholesterol metabolism may have a special benefit over some other strategies, Kovacs notes. "Many other drugs in development for Alzheimer’s target the secretases" – enzymes that cut the larger amyloid precursor protein into smaller fragments, including amyloid-beta. "Because secretases have normal functions, secretase inhibitors have to be tailored to selectively stop amyloid-beta production. Since they do not affect secretases, ACAT inhibitors may have fewer side effects." Kovacs is an assistant professor of Neurology at Harvard Medical School.

Sue McGreevey | EurekAlert!
Further information:
http://www.mgh.harvard.edu

More articles from Health and Medicine:

nachricht Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>