Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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


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:

More articles from Health and Medicine:

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences

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: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

TRAPPIST-1 planets provide clues to the nature of habitable worlds

21.03.2018 | Physics and Astronomy

The search for dark matter widens

21.03.2018 | Materials Sciences

Natural enemies reduce pesticide use

21.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>