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
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 noted.
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."
Newly created rats give insight
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 tasks.
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.
From studying the genetically engineered rats, the researchers have confirmed
the role of amyloid plaques in the development of the disease and discovered
specialised 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."
How the study was done
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 life
span, so 16-month-old rats are like people in their 40s and 2-month-olds are
like those in their 80s, Town noted.
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% 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 US
National Institute of Neurological Disorders and Stroke.
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