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

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
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 2,700+ scientific posters on ePosters
  • More Than 3,800+ 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 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

$21M Invested in Research Hubs in Developing Countries
The National Institutes of Health and other U.S. and Canadian partners are investing $20.9 million dollars over five years to establish seven regional research and training centers in low- and middle-income countries (LMICs).
Friday, October 09, 2015
NIH Breast Cancer Research to Focus On Prevention
A new phase of the Breast Cancer and the Environment Research Program (BCERP), focused on prevention, is being launched at the National Institutes of Health.
Friday, October 09, 2015
NIH Grantees Win 2015 Nobel Prize in Chemistry
The 2015 Nobel Prize in chemistry has been awarded to NIH grantees Paul Modrich, Ph.D., of the Howard Hughes Medical Institute and the Duke University School of Medicine, Durham, N.C.; and Aziz Sancar, M.D., Ph.D., of the University of North Carolina, Chapel Hill, N.C.,.
Thursday, October 08, 2015
NIH Announces High-Risk, High-Reward Research Awardees
NIH to fund 78 awards to support highly innovative biomedical research.
Wednesday, October 07, 2015
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Tuesday, October 06, 2015
NIH Funding Targets Gaps in Biomedical Research
New awards support emerging issues in cutting-edge biomedical research fields.
Tuesday, October 06, 2015
Scientists Test New Gene Therapy for Vision Loss from a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Tuesday, October 06, 2015
Dormant Viral Genes May Awaken to Cause ALS
NIH human and mouse study may open an unexplored path for finding treatments.
Thursday, October 01, 2015
Scientists Create World’s Largest Catalog of Human Genomic Variation
An international team of scientists from the 1000 Genomes Project Consortium has created the world’s largest catalog of genomic differences among humans, providing researchers with powerful clues to help them establish why some people are susceptible to various diseases.
Thursday, October 01, 2015
Drug Used To Treat HIV Linked to Lower Bone Mass in Newborns
NIH study finds mothers’ use of tenofovir tied to lower bone mineral content in babies.
Wednesday, September 30, 2015
Repairing Nerve Pathways With 3-D Printing
A novel 3-D printing approach was used to create custom scaffolds that helped damaged rat nerves regenerate and improved the animals’ ability to walk.
Tuesday, September 29, 2015
Bone Risks Linked to Genetic Variants
A large-scale genomic study uncovered novel genetic variants and led researchers to an unexpected gene that affects bone density and fracture risk.
Tuesday, September 29, 2015
Genetic Adaptations to Diet and Climate
Researchers found genetic variations in the Inuit of Greenland that reflect adaptations to their specific diet and climate.
Tuesday, September 29, 2015
NIH Launches Landmark Study On Substance Use And Adolescent Brain Development
Thirteen grants awarded to look at cognitive and social development in approximately 10,000 children.
Monday, September 28, 2015
Grants to Help Identify Variants in the Genome’s Regulatory Regions
New computational approaches needed to wade through millions of inherited DNA differences to find which ones matter.
Thursday, September 24, 2015
Scientific News
Breaking Through the Barriers to Lab Innovation
Here we examine the drivers behind the move for greater innovation, the challenges and current trends in laboratory informatics, and the tools that can be used to break these barriers.
Education and Expense: The Barriers to Mass Spectrometry in Clinical Laboratories?
Here we examine the perceived barriers to mass spec in clinical laboratories and explore the possible drivers behind the recent shift in uptake of the technology in clinical settings.
Fruit Fly Pheromone Flags Great Real Estate for Starting a Family
Finding could aid efforts to control mosquito-borne diseases like malaria by manipulating odorants
Gene Editing Could Enable Pig-To-Human Organ Transplant
The largest number of simultaneous gene edits ever accomplished in the genome could help bridge the gap between organ transplant scarcity and the countless patients who need them.
Antioxidants Cause Malignant Melanoma to Metastasize Faster
Fresh research at Sahlgrenska Academy has found that antioxidants can double the rate of melanoma metastasis in mice.
New Therapy Reduces Symptoms of Inherited Enzyme Deficiency
A phase three clinical trial of a new enzyme replacement medication, sebelipase alfa, showed a reduction in multiple disease-related symptoms in children and adults with lysosomal acid lipase deficiency, an inherited enzyme deficiency that can result in scarring of the liver and high cholesterol.
Adult High Blood Pressure Risk Identifiable in Childhood
Groups of people at risk of having high blood pressure and other related health issues by age 38 can be identified in childhood, new University of Otago research suggests.
Analyzing Protein Structures in Their Native Environment
Enhanced-sensitivity NMR could reveal new clues to how proteins fold.
Supercoiled DNA is Far More Dynamic Than the “Watson-Crick” Double Helix
Researchers have imaged in unprecedented detail the three-dimensional structure of supercoiled DNA, revealing that its shape is much more dynamic than the well-known double helix.
Mini-kidneys Successfully Grown from Stem Cells
Researchers from Murdoch Childrens Research Institute have perfected a method of turning stem cells into mini-kidneys for use in drug screening, disease modelling and cell therapy.
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
2,700+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos