"These
swellings represent structural damage that seemed to be well
established and stable, but clearing out the plaques often led to rapid
recovery of normal structure over a few days," says senior author David
H. Holtzman, M.D., the Charlotte and Paul Hagemann Professor and head
of the Department of Neurology. "This provides confirmation of the
potential benefits of plaque-clearing treatments and also gets us
rethinking our theories on how plaques cause nerve cell damage."
Prior to the experiment, Holtzman and some other scientists had
regarded plaque damage to nerve cells as a fait accompli--something
that the plaques only needed to inflict on nerve cells once. According
to Holtzman, the new results suggest that plaques might not just cause
damage but also somehow actively maintain it.
The study, will appear in the Feb. 5 issue of the Journal of Clinical
Investigation.
Lead author Robert Brendza, Ph.D., research instructor, began the
experiment with one key question: how did clearance of brain plaques,
made possible by the development of Abeta antibodies, affect the
progression of Alzheimer's disease? Through collaborations with
researchers at other institutions, he had acquired several key
techniques and technologies that allowed him to closely track changes
in live brain cells in mice with an Alzheimer's-like condition.
The mice he used for the study had two mutations. One, utilized by
scientists at Eli Lilly, causes amyloid plaques to build up, creating
the Alzheimer's-like
condition. The second, developed by scientists at
Washington University, causes some of the mouse brain cells to produce
a dye that allowed Brendza to obtain detailed images of nerve cell
branches.
To correlate brain cell changes with plaque development, Brendza
injected another dye, developed by scientists at the University of
Pittsburgh, that temporarily sticks to amyloid. He showed that as the
plaques appeared, nearby branches of nerve cells developed bumps and
swellings.
"If you look under the electron microscope at these swellings, they are
filled with abnormal amounts of different types of cellular parts known
as organelles," Holtzman explains. "Normally any given segment of a
nerve cell branch would have only very small amounts of these
organelles."
Nerve cells move organelles along their branches as a part of their
regular function. Holtzman suspects that this transport breaks down in
the mice, leading to pileups that become swellings. Scientists have
previously demonstrated that such swellings make it difficult or
impossible for nerve-cell branches to send signals.
After showing that the swellings were mostly stable in number and size
over the course of three to seven days, Brendza injected Abeta
antibodies directly onto the surface of the mouse brains. In the region
of the injection, the antibodies cleared the plaques, confirming
earlier research results. Then Brendza closely monitored the swellings
for three days.
"We thought that clearing the plaques would halt the progression of the
damage--stop the development of new swellings," says Brendza. "But what
we saw was much more striking: in just three days, there were 20 to 25
percent reductions in the number or size of the existing swellings."
The nerve cells' rapid ability to regain normal structure has Holtzman
and Brendza wondering if the nerve cells are constantly trying to
restore their normal structure. If so, that recuperative effort must
somehow be countered on an ongoing basis by the effects of th
e plaques.
More research is needed to determine if similar effects will occur in
humans. Abeta antibodies are currently being considered for use in
Alzheimer's patients in clinical trials.
In the mice, the largest swellings were least likely to heal. Brendza
plans to look into whether additional treatment can prompt their
recovery.
Holtzman and Brendza plan to continue using the mouse model to study
disease treatments and the cellular abnormalities caused by their
Alzheimer's-like condition.
"For example, we'd like to know what's going wrong in the nerve cell
branches that get these swellings," Holtzman says. "Is it really a
cellular transport problem, or do the swellings result from the
plaques' effects on nearby support cells? Or is it something else?"
'"/>
Source:
Related biology news :
1. Chemists create Superbowl molecule; May lead to better health
2. Inflammatory molecules released by pollen trigger allergies
3. Researchers discover molecule that causes secondary stroke
4. Yale researchers identify molecule for detecting parasitic infection in humans
5. Scientists identify molecule that regulates well-known tumor suppressor
6. Medical molecules designed to respond to visible light that can penetrate tissue
7. Researchers find promising cancer-fighting power of synthetic cell-signaling molecule
8. Chemists synthesize molecule that helps body battle cancers, malaria
9. DNA constraints control structure of attached macromolecules
10. Scripps research scientists identify infertility molecule
11. Scientists discover that three molecules may be developed into new Alzheimers drugs