Featured Research

from universities, journals, and other organizations

UCI Researchers Create First Living Model To Exhibit Both Signature Lesions Of Alzheimer's Disease

Date:
August 4, 2003
Source:
University Of California, Irvine
Summary:
A newly engineered, genetically altered mouse will allow researchers for the first time to study the two signature lesions of Alzheimer’s disease in a single organism — a model that closely matches how the disease develops in the human brain.

Irvine, Calif. — A newly engineered, genetically altered mouse will allow researchers for the first time to study the two signature lesions of Alzheimer’s disease in a single organism — a model that closely matches how the disease develops in the human brain. Created by UC Irvine neurobiologists Frank LaFerla and Salvatore Oddo, the mouse is expected to provide a better “living laboratory” for understanding how these lesions grow, aiding efforts to find an effective treatment for both the sporadic and inherited forms of the disease.

Related Articles


“For the first time, plaque and tangle lesion formations can be studied together, letting us understand the relationship between the two lesions and dissect the processes by which they may be connected,” said LaFerla, a professor of neurobiology and behavior, and senior author of the study, which appears in the July 31 issue of Neuron.

Plaque lesions grow on the outside of healthy cells, cutting off their ability to communicate with other cells, while tangle lesions grow inside of neural cells and clog signaling pathways. Plaque lesions are factors in the early-onset inherited and sporadic forms of the disease, and tangle lesions are found primarily in the sporadic form.

According to LaFerla, the mouse will be valuable in the search for drugs that can target both lesions. “This may eventually lead to a single class of drugs for treating both the inherited and sporadic forms of the disease,” he said. “We now have the ability to study a wider spectrum of Alzheimer’s disease than previously possible.”

LaFerla and Oddo created the mouse by genetically altering it to host three mutant human genes that foster lesion growth: beta-amyloid precursor protein (âAPP), presenilin-1 and tau. âAPP is the source of the beta-amyloid protein that forms into brain plaques, while presenilin-1 is needed for this protein to form. Tau is the critical component of tangles.

Using the triple-transgenic mouse, the UCI researchers have already traced the sequence of molecular events leading to the disease. Significantly, they found that beta-amyloid plaques appeared first in the mouse brain, and tau-laden tangles appeared later. This suggests that beta-amyloid may be the initiating component of both sporadic and familial Alzheimer’s disease.

“This finding confirms the human genetic data indicating that plaques are the earliest pathological feature of the disease,” said LaFerla.

The UCI researchers also found that beta-amyloid can accumulate in neural cells before plaques or tangles form. This appears to diminish the function of brain synapses, which may lead to memory impairments, the signature feature of Alzheimer’s disease. The researchers found this was the earliest pathological change that occurred in their mice and will further investigations into the condition in humans.

Alzheimer’s disease is the most common cause of dementia, afflicting more than four million Americans. The majority of Alzheimer’s cases are sporadic, striking individuals at random as opposed to running in families. Generally, the sporadic form afflicts individuals older than 65. A small percentage of cases are passed down from one generation to another and generally have a much earlier onset, usually in the 40s or 50s, but sometimes as young as 16 years of age. Other than the age of onset, both forms are fairly similar.

The National Institute for Aging and the Alzheimer’s Association funded the research.

About the triple-transgenic mouse

Transgenic mice have enabled researchers to observe experimentally what happens to an entire organism during the progression of a disease. In many areas, they are already the leading models for studying human diseases and their treatments.

To create these mice, UCI researchers injected foreign genetic material (generally, human genes harboring disease-causing mutations) into fertilized mouse eggs. When the mice were born, the ones producing the human proteins typically developed the designated traits or disease phenotype, and in the case for the mice in this study, the Alzheimer-type pathology.

Because mice don’t normally develop Alzheimer’s pathology, the only way to reproduce it in mice was to have them overproduce the human proteins associated with the disease. LaFerla and Oddo created the model for this study by injecting âAPP and tau genes into single-cell embryos from single-transgenic mice already harboring the presenilin-1 gene. This method assured that future generations would inherit the genetic material as one unit.

Because of this, the mice will be easy to breed and have the same genetic background. This is an important feature for analyzing the behavior of these mice and for evaluating drugs, since the researchers won’t have to worry about the confounding effects associated with mice with different genetic backgrounds. It is anticipated that this unique mouse model will prove to be extremely useful in the preclinical evaluation of potential Alzheimer drugs.


Story Source:

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


Cite This Page:

University Of California, Irvine. "UCI Researchers Create First Living Model To Exhibit Both Signature Lesions Of Alzheimer's Disease." ScienceDaily. ScienceDaily, 4 August 2003. <www.sciencedaily.com/releases/2003/08/030804075902.htm>.
University Of California, Irvine. (2003, August 4). UCI Researchers Create First Living Model To Exhibit Both Signature Lesions Of Alzheimer's Disease. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2003/08/030804075902.htm
University Of California, Irvine. "UCI Researchers Create First Living Model To Exhibit Both Signature Lesions Of Alzheimer's Disease." ScienceDaily. www.sciencedaily.com/releases/2003/08/030804075902.htm (accessed October 24, 2014).

Share This



More Plants & Animals News

Friday, October 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Reuters - Innovations Video Online (Oct. 24, 2014) — Miniature deep sea animals discovered off the Australian coast almost three decades ago are puzzling scientists, who say the organisms have proved impossible to categorise. Academics at the Natural History of Denmark have appealed to the world scientific community for help, saying that further information on Dendrogramma enigmatica and Dendrogramma discoides could answer key evolutionary questions. Jim Drury has more. Video provided by Reuters
Powered by NewsLook.com
Black Bear Cub Goes Sunday Shopping

Black Bear Cub Goes Sunday Shopping

Reuters - Light News Video Online (Oct. 23, 2014) — Price check on honey? Bear cub startles Oregon drugstore shoppers. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Dances With Wolves in China's Wild West

Dances With Wolves in China's Wild West

AFP (Oct. 23, 2014) — One man is on a mission to boost the population of wolves in China's violence-wracked far west. The animal - symbol of the Uighur minority there - is under threat with a massive human resettlement program in the region. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
Breakfast Debate: To Eat Or Not To Eat?

Breakfast Debate: To Eat Or Not To Eat?

Newsy (Oct. 23, 2014) — Conflicting studies published in the same week re-ignited the debate over whether we should be eating breakfast. Video provided by Newsy
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

 

Plants & Animals

Earth & Climate

Fossils & Ruins

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