Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

NIH-funded Researchers Create Next-Generation Alzheimer’s Disease Model

Published: Thursday, April 11, 2013
Last Updated: Thursday, April 11, 2013
Bookmark and Share
New rat model will advance Alzheimer’s research.

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.

“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.

Corriveau continued, “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.

Buckholtz continued, “Accordingly, Dr. Town and his colleagues are working towards making their new rat model easily accessible to the research community.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,300+ scientific posters on ePosters
  • More Than 4,900+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Researchers Develop Software That Could Facilitate Drug Development
AptaTRACE can identify aptamers, potentially speed drug advancement.
Saturday, July 30, 2016
NIH Funds Precision Medicine
NIH have committed roughly $31M to launch a new program for Transdisciplinary Collaborative Centers for health disparities research.
Friday, July 29, 2016
Zika Vaccine Candidates Show Promise
Two experimental vaccines have shown promise against a major viral strain responsible for the Brazilian Zika outbreak.
Friday, July 29, 2016
New Medication Shows Promise Against Liver Fibrosis in Animal Studies
Liver fibrosis is a gradual scarring of the liver that puts people at risk for progressive liver disease and liver failure.
Thursday, July 28, 2016
NIH Begins Yellow Fever Vaccine Trial
NIH has initiated an early-stage clinical trial of a vaccine to protect against yellow fever.
Thursday, July 28, 2016
Targeting Autoimmunity
Researchers have developed a strategy to treat a rare autoimmune disease which could lead to treatments of other autoimmune diseases.
Wednesday, July 27, 2016
Molecule May Affect Gaucher, Parkinson's Disease
Research has identified a molecule that restores activity of a dysfunctional enzyme linked to Gaucher and Parkinson's disease.
Wednesday, July 27, 2016
Uncovering Rhinovirus C Structure
Researchers have determined the structure of rhinovirus C. Their findings may aid the development of antiviral therapies and vaccines.
Wednesday, July 27, 2016
Vaccine Strategy Targets Multiple Influenza Viruses
Scientists have identified vaccine-induced antibodies that can neutralize strains of influenza virus that infect humans.
Monday, July 25, 2016
Connectome Map More Than Doubles Human Cortex’s Known Regions
Researchers at NIH have developed software that automatically detects the “fingerprint” of each of these areas in an individual’s brain scans.
Saturday, July 23, 2016
Uncovering a New Principle in Chemotherapy Resistance in Breast Cancer
The NIH study has revealed an entirely unexpected process for acquiring drug resistance that bypasses the need to re-establish DNA damage repair in breast cancers that have mutant BRCA1 or BRCA2 genes.
Thursday, July 21, 2016
Brain Circuits Helps People Cope With Stress
Researchers at NIH have identified brain patterns in humans that appear to underlie “resilient coping,” to stress that help some people handle stressful situations better than others.
Wednesday, July 20, 2016
NIH Investment Into HIV Research Expands
Funding has been awarded to six research teams to lead collaborative investigations worldwide toward an HIV cure.
Thursday, July 14, 2016
Treatment Advancement for Gaucher and Parkinson's Diseases
NIH scientists identify molecule that may act as a possible treatment of neurological diseases.
Wednesday, July 13, 2016
Use it or Lose it: Visual Activity Regenerates Links Between Eye, Brain
The mouse study is first to show visual stimulation helps re-wire visual system and partially restores sight.
Tuesday, July 12, 2016
Scientific News
Breakthrough Flu Vaccine Inhibited by Pre-existing Antibodies
Universal truths – how existing antibodies are sabotaging the most promising new human flu vaccines.
Researchers Develop Software That Could Facilitate Drug Development
AptaTRACE can identify aptamers, potentially speed drug advancement.
Gene Therapy for Metabolic Liver Diseases
Researchers have tested gene therapy in pigs from hereditary tyrosinemia type 1, with corrected liver cells being transplanted into the diseased liver.
Zika Vaccine Candidates Show Promise
Two experimental vaccines have shown promise against a major viral strain responsible for the Brazilian Zika outbreak.
New Medication Shows Promise Against Liver Fibrosis in Animal Studies
Liver fibrosis is a gradual scarring of the liver that puts people at risk for progressive liver disease and liver failure.
Raw Eggs Deemed Safe to Eat
A report published today by the Advisory Committee on the Microbiological Safety of Food (ACMSF) into egg safety has shown a major reduction in the risk from salmonella in UK eggs.
Monitoring TTX Toxin in Shellfish
In a number of small studies, mussels and oysters from the eastern and northern part of the Oosterschelde in Holland were found to contain tetrodotoxin (TTX).
Gene Terapy for Muscle Wasting Developed
New gene therapy could save millions of people suffering from muscle wasting disease.
NIH Begins Yellow Fever Vaccine Trial
NIH has initiated an early-stage clinical trial of a vaccine to protect against yellow fever.
Gene-Editing 'Toolbox' Targets Multiple Genes Simultaneously
Researchers have designed a system that modifies, or edits, multiple genes in a genome at once while minimising unintentional effects.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!