Featured Research

from universities, journals, and other organizations

Gladstone Study Reveals How Genetic Factor May Increase Risk For Alzheimer's Disease

Date:
March 25, 2004
Source:
University Of California - San Francisco
Summary:
Researchers at the Gladstone Institute of Neurological Disease have identified processes that may explain how a key protein, apolipoprotein E4 (apoE4), contributes to the development of Alzheimer's disease.

Researchers at the Gladstone Institute of Neurological Disease have identified processes that may explain how a key protein, apolipoprotein E4 (apoE4), contributes to the development of Alzheimer's disease. Their findings, described in the Journal of Neuroscience (March 10, 2004), include identifying where in the brain apoE4 is broken down into toxic fragments that can impair the function and survival of nerve cells. Results of their study may point the way to a new therapeutic strategy for the prevention and treatment of Alzheimer's disease.

Related Articles


ApoE4 is the best known genetic risk factor for Alzheimer's disease, but, until now, the mechanism by which it increases that risk has remained a mystery. The key finding of the current study relates to apoE4's tendency to be broken down into toxic fragments when it is produced in neurons, the brain cells responsible for cognitive functions.

Proteins can be broken into small pieces by enzymes known as proteases in a process termed proteolysis. While the degradation of proteins is important for many cell processes, it can be harmful when it occurs inappropriately, not only because it destroys the protein, but also because abnormally high levels of fragments can damage cells.

In the new study, involving the examination of genetically engineered mice, Gladstone researchers have established that:

* only apoE4 produced by neurons is susceptible to fragmentation, unlike apoE4 produced by other brain cells;

* fragmentation is correlated with age, occurring more frequently the older the animal, similar to the effect of age on Alzheimer disease risk in humans;

* fragmentation of apoE4 occurs predominantly in the very parts of the brain that are most vulnerable to Alzheimer's disease, the neocortex and hippocampus. In contrast, fragmentation does not occur in the cerebellum, which is much less vulnerable to Alzheimer's disease;

* the apoE4 fragments cause an abnormal change to the protein tau, which is also heavily affected by Alzheimer's disease. Both apoE4 fragments and Alzheimer's disease lead to the abnormal attachment of phosphate groups on tau that can end up contorting the shape of brain cells.

The investigators suspect that the fragmentation of apoE4 is caused by a neuron-specific enzyme, which they are now trying to identify and block with drugs.

"From this and our previous studies, we believe that the protease that cleaves apoE4 may serve as a therapeutic target for the prevention and treatment of Alzheimer's disease, especially in patients who are impacted by apoE4," said the senior author of the study, Yadong Huang, MD, PhD, staff research investigator at the Gladstone Institute of Neurological Disease (GIND) and assistant professor of pathology at the University of California, San Francisco (UCSF).

"With this work, we're a significant step closer to solving the key riddle of apoE4, namely, what is occurring at the molecular level that makes this protein so active in causing neurodegenerative disease," explained Dr. Robert Mahley, "Research of this kind is essential for the development of better treatments for Alzheimer's disease."

###

This work was supported in part by grants from the National Institutes of Health and by a MetLife Foundation award. The paper, "Neuron-Specific Apolipoprotein E4 Proteolysis Is Associated with Increased Tau Phosphorylation in Brains of Transgenic Mice," was co-authored by Gladstone Institute of Neurological DiseaseGIND staff members Walter J. Brecht, senior research associate; Faith M. Harris, research associate; Shengjun Chang, postdoctoral fellow; Ina Tesseur, postdoctoral fellow; Gui-Qiu Yu, senior research associate; Qin Xu, postdoctoral fellow ; Jo Dee Fish, research technologist; Tony Wyss-Coray, former staff research investigator; Manuel Buttini, former research scientist; and Lennart Mucke, GIND director and senior investigator, UCSF professor of neurology, along with Mahley and Huang.

The Gladstone Institute of Neurological Disease is one of three research institutes of The J. David Gladstone Institutes, a private, nonprofit biomedical research institution affiliated with UCSF. For further information, visit http://www.gladstone.ucsf.edu.


Story Source:

The above story is based on materials provided by University Of California - San Francisco. Note: Materials may be edited for content and length.


Cite This Page:

University Of California - San Francisco. "Gladstone Study Reveals How Genetic Factor May Increase Risk For Alzheimer's Disease." ScienceDaily. ScienceDaily, 25 March 2004. <www.sciencedaily.com/releases/2004/03/040324070926.htm>.
University Of California - San Francisco. (2004, March 25). Gladstone Study Reveals How Genetic Factor May Increase Risk For Alzheimer's Disease. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2004/03/040324070926.htm
University Of California - San Francisco. "Gladstone Study Reveals How Genetic Factor May Increase Risk For Alzheimer's Disease." ScienceDaily. www.sciencedaily.com/releases/2004/03/040324070926.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins