Islamabad, Feb 6 : One
of the most distinctive signs of the development of Alzheimer's disease is a
change in the behavior of a protein that neuroscientists call tau.
In
normal brains, tau is present in individual units essential to neuron health. In
the cells of Alzheimer's brains, by contrast, tau proteins aggregate into
twisted structures known as "neurofibrillary tangles."
These tangles are
considered a hallmark of the disease, but their precise role in Alzheimer's
pathology has long been a point of contention among researchers.
Now,
University of Texas Medical Branch at Galveston researchers have found new
evidence that confirms the significance of tau to Alzheimer's. Instead of
focusing on tangles, however, their work highlights the intermediary steps
between a single tau protein unit and a neurofibrillary tangle -- assemblages of
two, three, four, or more tau proteins known as "oligomers," which they believe
are the most toxic entities in Alzheimer's.
"What we discovered is that
there are smaller structures that form before the neurofibrillary tangles, and
they are much more toxic than the big structures," said Rakez Kayed, UTMB
assistant professor and senior author of a paper on the work now online in the
FASEB Journal. "And we established that they were toxic in real human brains,
which is important to developing an effective therapy."
According to
Kayed, a key antibody developed at UTMB called T22 enabled the team to produce a
detailed portrait of tau oligomer behavior in human brain tissue. Specifically
designed to bond only to tau oligomers (and not lone tau proteins or
neurofibrillary tangles), the antibody made it possible for the researchers to
use a variety of analytical tools to compare samples of Alzheimer's brain with
samples of age-matched healthy brain.
"One thing that's remarkable about
this research is that before we developed this antibody, people couldn't even
see tau oligomers in the brain," Kayed said. "With T22, we were able to
thoroughly characterize them, and also study them in human brain
cells."
Among the researchers' most striking findings: in some of the
Alzheimer's brains they examined, tau oligomer levels were as much as four times
as high as those found in age-matched control brains.
Other experiments
revealed specific biochemical behavior and structures taken on by oligomers, and
demonstrated their presence outside neurons -- in particular, on the walls of
blood vessels.
"We think this is going to make a big impact
scientifically, because it opens up a lot of new areas to study," Kayed said.
"It also relates to our main focus, developing a cure for Alzheimer's. And I
find that very, very exciting."
Ends
SA/EN
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