Featured Research

from universities, journals, and other organizations

Researchers create next-generation Alzheimer's disease model

Date:
April 9, 2013
Source:
NIH/National Institute of Neurological Disorders and Stroke
Summary:
A new genetically engineered lab rat that has the full array of brain changes associated with Alzheimer's disease supports the idea that increases in a molecule called beta-amyloid in the brain causes the disease.

Beta-amyloid molecules (green) surround dying neurons (red) in the brains of a new rat model of Alzheimer's disease.
Credit: Courtesy of Town lab, Zilkha Neurogenetic Institute at the University of Southern California Keck School of Medicine.

A new genetically engineered lab rat that has the full array of brain changes associated with Alzheimer's disease supports the idea that increases in a molecule called beta-amyloid in the brain causes the disease, according to a study, published in the Journal of Neuroscience. The study was supported by the National Institutes of Health.

Related Articles


"We believe the rats will be an excellent, stringent pre-clinical model for testing experimental Alzheimer's disease therapeutics," said Terrence Town, Ph.D., the study's senior author and a professor in the Department of Physiology & Biophysics in the Zilkha Neurogenetic Institute at the University of Southern California Keck School of Medicine, Los Angeles.

Alzheimer's is an age-related brain disorder that gradually destroys a person's memory, thinking, and the ability to carry out even the simplest tasks. Affecting at least 5.1 million Americans, the disease is the most common form of dementia in the United States. Pathological hallmarks of Alzheimer's brains include abnormal levels of beta-amyloid protein that form amyloid plaques; tau proteins that clump together inside neurons and form neurofibrillary tangles; and neuron loss. Additionally, glial cells -- which normally support, protect, or nourish nerve cells -- are overactivated in Alzheimer's.

Plaque-forming beta-amyloid molecules are derived from a larger protein called amyloid precursor protein (APP). One hypothesis states that increases in beta-amyloid initiate brain degeneration. Genetic studies on familial forms of Alzheimer's support the hypothesis by linking the disease to mutations in APP, and to presenilin 1, a protein thought to be involved in the production beta-amyloid.

Researchers often use rodents to study diseases. However, previous studies on transgenic mice and rats that have the APP and presenilin 1 mutations only partially reproduce the problems caused by Alzheimer's. The animals have memory problems and many plaques but none of the other hallmarks, especially neurofibrillary tangles and neuron loss.

To address this issue, Dr. Town and his colleagues decided to work with a certain strain of rats.

"We focused on Fischer 344 rats because their brains develop many of the age-related features seen in humans," said Dr. Town, who conducted the study while working as a professor of Biomedical Sciences at Cedars-Sinai Medical Center and David Geffen School of Medicine at the University of California, Los Angeles.

The rats were engineered to have the mutant APP and presenilin 1 genes, which are known to play a role in the rare, early-onset form of Alzheimer's. Behavioral studies showed that the rats developed memory and learning problems with age. As predicted, the presence of beta-amyloid in the brains of the rats increased with age. However, unlike previous rodent studies, the rats also developed neurofibrillary tangles.

"This new rat model more closely represents the brain changes that take place in humans with Alzheimer's, including tau pathology and extensive neuronal cell death," said Roderick Corriveau, Ph.D., a program director at NIH's National Institute of Neurological Disorders and Stroke. "The model will help advance our understanding of the various disease pathways involved in Alzheimer's onset and progression and assist us in testing promising interventions."

The researchers performed a variety of experiments confirming the presence of neurofibrillary tangles in brain regions most affected by Alzheimer's such as the hippocampus and the cingulate cortex, which are involved in learning and memory. Further experiments showed that about 30 percent of neurons in these regions died with age, the largest amount of cell death seen in an Alzheimer's rodent model, and that some glial cells acquired shapes reminiscent of the activated glia found in patients.

"Our results suggest that beta-amyloid can drive Alzheimer's in a clear and progressive way," said Dr. Town.

Activation of glia occurred earlier than amyloid plaque formation, which suggests Dr. Town and his colleagues identified an early degenerative event and new treatment target that scientists studying other rodent models may have missed.

The findings support a prime research objective identified during the May 2012, NIH-supported Alzheimer's Disease Research Summit 2012: Path to Treatment and Prevention, an international gathering of Alzheimer's researchers and advocates. Improved animal models were cited as key to advancing understanding of this complex disease.

"To fully benefit from this exciting new work, there is a critical need to share the animal model with researchers dedicated to finding ways to delay, prevent or treat Alzheimer's disease'' said Neil Buckholtz, Ph.D., of the National Institute on Aging, which leads the NIH effort in Alzheimer's research. "Accordingly, Dr. Town and his colleagues are working towards making their new rat model easily accessible to the research community."

In addition to grants from NINDS (NS076794), NIA (AG029726, AG033394) and the NIMH Intramural Research Program, this study was funded by the Alzheimer's Association (IIRG-05-14993, ZEN-10-174633) and the Ellison Foundation/American Federation for Aging Research (M11472).


Story Source:

The above story is based on materials provided by NIH/National Institute of Neurological Disorders and Stroke. Note: Materials may be edited for content and length.


Journal Reference:

  1. Cohen RM et al. A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric Aβ and frank neuronal loss. Journal of Neuroscience, April 10, 2013 DOI: 10.1523/JNEUROSCI.3672-12.2013

Cite This Page:

NIH/National Institute of Neurological Disorders and Stroke. "Researchers create next-generation Alzheimer's disease model." ScienceDaily. ScienceDaily, 9 April 2013. <www.sciencedaily.com/releases/2013/04/130409173455.htm>.
NIH/National Institute of Neurological Disorders and Stroke. (2013, April 9). Researchers create next-generation Alzheimer's disease model. ScienceDaily. Retrieved November 23, 2014 from www.sciencedaily.com/releases/2013/04/130409173455.htm
NIH/National Institute of Neurological Disorders and Stroke. "Researchers create next-generation Alzheimer's disease model." ScienceDaily. www.sciencedaily.com/releases/2013/04/130409173455.htm (accessed November 23, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Sunday, November 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. Video provided by Newsy
Powered by NewsLook.com
You Don't Have To Be Alcohol Dependent To Need Treatment

You Don't Have To Be Alcohol Dependent To Need Treatment

Newsy (Nov. 21, 2014) A study by the Centers for Disease Control and Prevention found 9 out of 10 excessive drinkers in the country are not alcohol dependent. Video provided by Newsy
Powered by NewsLook.com
Your Complicated Job Might Keep Your Brain Young

Your Complicated Job Might Keep Your Brain Young

Newsy (Nov. 20, 2014) Researchers at the University of Edinburgh found the more complex your job is, the sharper your cognitive skills will likely be as you age. 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


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