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 Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

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: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

New pop-up strategy inspired by cuts, not folds

27.02.2017 | Materials Sciences

Sandia uses confined nanoparticles to improve hydrogen storage materials performance

27.02.2017 | Interdisciplinary Research

Decoding the genome's cryptic language

27.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>