Scientists Make Strides in Charting Development of Alzheimer's
Washington, Nov. 23 (Bloomberg) -- New developments in
imaging and genetic technology could help doctors to chart the
course of Alzheimer's disease, according to the results of two
studies.
Researchers at Duke University Medical Center have developed
a new type of high-resolution imaging system that helps doctors
see tangled protein plaques, which typically form in the brains
of Alzheimer's patients. The plaques, which are thought to either
contribute to, or arise from, the disease, previously could only
be seen in one dimension, by placing stained tissue samples under
a microscope.
''If you can visualize the plaque in vivo to see how its
development relates to cognitive behavior, you can answer the
question of cause and effect,'' said Helene Benveniste, a Duke
anesthesiologist who led the study.
In Alzheimer's disease, normal proteins in the brain are
broken down to form dangerous plaques. Over time, those plaques
build up, which researchers believe leads to the neurological
breakdown seen in Alzheimer's.
In order to make the images of the plaques, the doctors took
brain samples from patients who had just died of Alzheimer's, so
the tissues were still fresh. The ''brain plugs'' were analyzed
at different angles in order to create a blended, three-
dimensional image of the plaques.
The study, which could help doctors to understand the way
Alzheimer's disease progresses, was published in today's edition
of the Proceedings of the National Academy of Sciences.
Exploiting Technologies
The new imaging technique was made possible by exploiting
and combining powerful existing technologies like magnetic
resonance imaging, known commonly as MRI, and computers, in order
to create a reliable picture.
''When reconstituted in a 3D image, plaques look like small
round balls, basically spots of garbage, floating in space,''
Benveniste said.
Still, the researchers said that the new imaging technique
isn't useful for diagnosing Alzheimer's disease in human
patients. Currently, the only way to determine if someone has
Alzheimer's is to extensively examine the brain tissue of a
person who has already died.
However, the researchers are hopeful that the technique
could be used as a research tool to investigate the course of the
disease in animals that have been genetically engineered to
produce large quantities of human plaque proteins.
For example, by using genetically engineered mice that
produce human protein plaques in their brains, researchers say
that they might be able to chart the growth and development of
the plaques through time, and observe the ways in which plaques
respond to new drugs.
''The dream of every brain researcher is to be able to
follow, over time, both development of brain disease and the
effects of drugs designed to combat them,'' Benveniste said. ''If
it works for this disease, it could work for other disorders and
therapies. Time will tell.''
Transgenic Mice
In a separate study, researchers reported that they have
developed a new strain of mice that are engineered to produce
tangled strands of a special human protein, called ''tau,'' which
is known to be involved in the development of Alzheimer's and
other neurodegenerative diseases.
Tau, along with another protein, dubbed ''beta amyloid'' are
the two signature markers of the disease.
''This mouse isn't, in and of itself, a complete model for
Alzheimer's disease, but it should help us to better understand
the crucial role that tau tangles play in the progression of that
disease'' and others, said Virginia Lee, a professor of
Alzheimer's research at the University of Pennsylvania Medical
Center, the study's lead author.
In order to create a more accurate model system for
Alzheimer's progression in humans, the researchers are currently
mating the new type of mouse with an existing strain that has
been engineered to produce human beta amyloid plaques. That means
that the progeny of the two types of mice would have both tau and
beta amyloid in their brains. This would be a very accurate model
of Alzheimer's in humans, the team said.
The report describing the ''tau mouse'' will be published in
tomorrow's edition of the journal Neuron.
Looks Promising
The researchers observed the new strain of tau-producing
mice and said that it looked promising because the mice had
difficulty moving, which is a symptom of neurological
malfunctioning. In addition, as they aged, the mice produced more
and more tau in their brains, a hallmark symptom of Alzheimer's
disease.
The researchers hope that the new mice might be able to shed
light on the role played by tau in the development of Alzheimer's
in humans.
''Tau has not been as highly regarded as a player as beta
amyloid in the mechanisms of brain degeneration associated with
Alzheimer's disease,'' said John Trojanowski, a professor of
pathology at the University of Pennsylvania, who co-authored the
study. ''Some of us, however, have long believed that tau may be
directly responsible for the death of neurons'' in Alzheimer's
and other brain diseases, he said.
Imperfect Model
The model is not perfect, however. In humans, tau tangles
are formed by two long tau particles winding around each other,
like twisted yarn. In the mice, however, the tangles are made up
of straight single strands of tau, the researchers said. Also,
the location of most tau tangles in the mice -- in the spinal
cord and brain stem -- more closely mimics the distribution of
the proteins in other neurodegenerative human diseases like
Parkinson's disease and hereditary forms of dementia.
Researchers are still unsure about the cause of Alzheimer's
disease, a degenerative neurological disease that strikes
4 million Americans.
Much research, has centered around a theory known as the
''amyloid hypothesis'' that holds that eliminating the protein
plaques that build up in the brains of patients with Alzheimer's
will cure the disease.
Elan Corp. is currently developing a vaccine that trains the
immune system to clear the protein plaques out of the brain.
Drugs now on the market, including Pfizer Inc. and Eisai
Co.'s Aricept and Warner-Lambert Co.'s Cognex, only treat the
symptoms of the disease.
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