WEDNESDAY, April 10 (HealthDay News) -- Everyone wants to build
a better mousetrap, but researchers working to uncover the secrets
of Alzheimer's disease have taken that a step further: They've
built a better rat.
By creating genetically engineered lab animals that more closely
mirror key elements of Alzheimer's in the human brain, scientists
report they have created a more effective, faster approach for
early testing of potential drugs to treat the disease.
These "transgenic" rats are better lab animals than are other
rodents for a variety of reasons, according to study author
Terrence Town, a professor in the physiology and biophysics
department at the Keck School of Medicine at the University of
Southern California. "You get so much more usable data from these
"First, the typical rat, which is 5 million years closer to the
human than the mouse is, is a better model for pathology than the
mouse," Town said. Mice have typically been seen as the preferred
lab animal because rats are four times more expensive to house, he
Because the genetically altered rats are designed to develop
specific pathologies seen in Alzheimer's, these rodents could help
researchers better understand the disease process and test new
therapeutics, he explained. "With mice models, you can cure them
with lots of things but none have translated to humans, and we
believe we're now going to close the gap with these rats."
Alzheimer's disease, which affects at least 5.1 million
Americans, is an age-related dementia that gradually destroys a
person's memory, thinking and the ability to carry out simple
Scientists have found that brain evidence of the disease
includes the loss of neurons, or nerve cells; the development of
abnormal levels of proteins that form what are called amyloid
plaques, and the clumping of "tau proteins" inside neurons, forming
what are termed "neurofibrillary tangles."
The newly created transgenic rats are the first rodents to have
mutations that effectively reproduce those brain changes, according
to the research published April 9 in the
Journal of Neuroscience.
From studying the genetically engineered rats, the researchers
have confirmed the role of amyloid plaques in the development of
the disease and discovered specialized glial cells (neural support
cells) before the development of amyloid plaque. That suggests that
activation of those cells could potentially become a new treatment
target, according to Town. "We may be able to see subtle changes in
humans earlier than we thought in people who are predisposed to
To create a transgenic rat, "you take a disease-causing gene
from a human and you put it into an animal," Town explained. "You
make a line of animals, just like you would with dogs or horses, to
transmit that gene."
The scientists then test to be sure the rat progeny have
evidence of the genetic changes and allow them to age. Rats
typically have a three-year lifespan, so 16-month-old rats are like
people in their 40s and 2-month-olds are like those in their 80s,
The researchers tested the transgenic rats to confirm the
presence of the neurofibrillary tangles in areas of the brain
involved in learning and memory. They also found evidence that 30
percent of the rats' brain neurons in these areas died as the rats
aged, with some glial cells forming themselves into shapes similar
to those found in human patients.
Heather Snyder, director of medical and scientific operations
for the Alzheimer's Association, said the research represents the
first time critical processes and pathologies of the disease have
been replicated in an animal model. But she warned that animal
models are limited.
"Rats are not humans and animals do not develop Alzheimer's,"
Snyder noted. "This is something that is still being manipulated by
the scientists -- animal models are an early tool in research. So,
while this type of research and this type of advance in the field
is important, this is still basic science."
Town said his hope is that the transgenic rats will help
researchers uncover principles applicable to other neurological
diseases, such as amyotrophic lateral sclerosis -- also known as
ALS or Lou Gehrig's disease -- and Parkinson's disease. "As we make
this model available to the research community, our hope is that it
will be useful in basic research and treatment development," he
Learn more about Alzheimer's disease from the
U.S. National Institute of Neurological Disorders and