Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gladstone scientists prove neurons produce Alzheimer’s-linked apolipoprotein E

11.05.2006


Unique mouse model helps solve protein mystery



A question long debated among Alzheimer’s disease researchers has been definitively answered by scientists at the Gladstone Institute of Neurological Disease in San Francisco.

Using a unique mouse model, Gladstone Investigator Yadong Huang, MD, PhD, and his team have proven that, under certain conditions, neurons produce Alzheimer’s-linked apolipoprotein E.


Also known as apoE, this cholesterol-carrying protein has three common forms, one of which, apoE4, is the major known genetic risk factor for Alzheimer’s disease, according to studies published around the world in recent years. Until now, most researchers have believed that apoE is synthesized in the brain solely in such cells as astrocytes, microglia, and ependymal layer cells. Controversial for the last decade has been the question of whether or not neurons, which make thought and memory possible by transmitting electrical signals, can produce apoE.

The Gladstone study, published in the May 10 issue of the Journal of Neuroscience and highlighted in its "This Week in the Journal" section, proves that neurons, too, produce apoE, but only in response to injury to the brain.

Key to the finding has been the development of a mouse model that is uniquely capable of alerting researchers whenever and wherever the apoE gene is expressed. Huang and his team have succeeded in making one of the two alleles of the apoE gene produce a green fluorescent protein that represents apoE, while the remaining allele functions normally. Thus, under a microscope, the bright green fluorescence, dubbed EGFPapoE, shows researchers wherever the apoE gene is expressed.

"This study lays to rest a long-standing controversy concerning the neuronal expression of apoE," says senior author Huang, an assistant professor of pathology and neurology at UCSF. "Our study proves clearly that neurons produce apoE in response to injury. They support the notion that an understanding of how apoE expression is regulated in neurons is important for unraveling the mechanisms underlying apoE4-related neurodegenerative disorders."

"ApoE expression can be detected with unprecedented sensitivity and resolution in these mice," explains Qin Xu, PhD, a Gladstone postdoctoral scholar and first author of the paper. "This mouse model, known as the ’EGFP knock-in,’ is a new and extremely promising approach to monitor gene expression in vivo." "Our EGFPapoE reporter mice can be used to track apoE expression in any tissue at any stage of development," adds Huang. "They will be a valuable tool for investigating the normal functions of apoE and the regulatory mechanisms that govern its expression."

Still to be determined is the exact mechanism by which apoE4 wreaks havoc on the brain, playing roles not only in Alzheimer’s disease but also in a number of other neurological diseases. Studies in Huang’s lab have revealed a possible scenario. It appears that apoE in neurons is subject to processing by an enzyme that clips off a portion of the protein, resulting in toxic fragments that escape the secretory pathway and enter the cytosol (the fluid portion of a cell’s cytoplasm). Studies now underway at Gladstone and elsewhere indicate that those fragments may interfere with glucose metabolism in the mitochondria (small intracellular organelles responsible for energy production, among other functions), leading to mitochondrial dysfunction and neuronal cell death.

The paper, "Profile and Regulation of Apolipoprotein (Apo) E Expression in Central Nervous System in Mice with Targeting of Green Fluorescent Protein Gene to the apoE Locus," was authored by Aubrey Bernardo, David Walker, and Tiffany Kanegawa of the Gladstone Institute of Neurological Disease, Gladstone Institutes President Robert W. Mahley, and Xu and Huang. This work was supported in part by grants from the National Institutes of Heath and a postdoctoral fellowship from the John Douglas French Alzheimer’s Foundation.

John Watson | EurekAlert!
Further information:
http://www.gladstone.ucsf.edu
http://www.ucsf.edu

More articles from Health and Medicine:

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

nachricht High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University

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: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>