Alzheimer’s disease does
not strike immediately the person, like stroke. The signs of the cognitive impairment
start to show one as warning signals, and little-by-little the disease takes
its toll with compete capture of the patient’s mind. Therefore, it brings the
association that Alzheimer’s disease seems to spread like an infection from
brain cell to brain cell, capturing more and more areas of the human brain. Several
new studies have confirmed that this intuitive assertion is not so far-fetched.
But instead of common viruses or bacteria, the core of the process is being associated
with distorted protein known as tau.
For some time, scientists have more or less clear picture of how Alzheimer's
Disease affects the brain. Certain mutations may lead to an increased
production of a protein called amyloid beta in the region of the brain that
creates memory. This excess amyloid beta, naturally secreted by brain cells
then becomes a complex called an oligomer. These oligomers may interrupt the
signals transmitted between neurons. As in other neurodegenerative diseases
like Parkinson's or Huntington's, the spread of oligomers appears to be driving
the disease process.
Oligomer-linked diseases are relatively common, in part because
oligomers can also play an essential biological role in the brain. A recent investigation
using fruit flies reveals that the presence of a specific oligomer is actually
required for the flies to form long-term memories.
In an early stage of Alzheimer's, the naturally secreted amyloid beta
protein builds up as oligomers in the brain, which then go on to form larger
aggregates called plaques. Later in the disease, another aberrant form of a
protein called tau starts to build up, in the entorhinal cortex. Normally, tau
helps provide structure crucial to neuron functioning. The buildup of tau,
however, causes the protein to tangle and eventually kill brain cells.
Alzheimer’s researchers
have long known that dying, tau-filled cells first emerge in a small area of
the brain where memories are made and stored. The disease then slowly moves
outward to larger areas of the brain that involve remembering and reasoning.
But for more than a
quarter century, they have been unable to decide between two explanations. The
spread might mean that the disease is transmitted from neuron to neuron,
perhaps along the paths nerve cells use to communicate with one another. Or it
could mean that some brain areas are more resilient than others and so resist
the disease longer.
The new studies provide
an answer. And they indicate that it might be possible to bring a patient’s
Alzheimer’s disease to an abrupt halt very early in its course by preventing
this cell-to-cell transmission, perhaps with an antibody that blocks tau.
The studies, done
independently by researchers at Columbia and Harvard universities, involved
genetically engineered mice that could make abnormal human tau proteins
predominantly in the entorhinal cortex, a sliver of tissue behind the ears
toward the middle of the brain, where cells first start dying in Alzheimer’s
disease.
As expected, tau showed
up there. And, as expected, entorhinal cortex cells in the animals started
dying, filled with tangled, spaghetti-like strands of tau.
Over the next two years,
the cell death and destruction spread outward to other cells that are part of
the same nerve cell network. Because those other cells could not make human
tau, the only way they could get the protein was by transmission from nerve
cell to nerve cell.
Karen Duff, a professor at the Taub Institute for Alzheimer’s Disease
Research at Columbia University, claimed that environment could be playing a
role in where tau appears in the brains of the mice. But she says the animals
were bred to express human tau in only one part of the brain, and that human
tau’s appearance in other parts of the brain therefore strongly suggest the
protein jumped, or transferred somehow from cell to cell. Supporting her case,
she says, is precedent from Parkinson’s models showing that a protein critical
to that neurodegenerative disease, synuclein, also moves from cell to cell. “We
designed experiments to tell if the cell is upregulating its own production of
tau, as a result of being in the same environment of the cells making human
tau,” she says. “And we came to the conclusion that the tau was spreading. We
suspect that the original cell dies, and the tau is picked up by neighboring
cells.”
Understanding how this protein moves may allow scientists to stop tau
in its tracks. "This opens up a whole new world of biology," says Karen
Duff. Tau is implicated in 30 different forms of dementia. In addition,
the movement of tau may be similar to the spread of oligomers associated with
Parkinson's and Huntington's. Nonetheless, we are still a long way from a
therapeutic solution and stopping tau, which comes at a relatively late stage
of Alzheimer's, might be a very limited therapy”.
"If, as our data
suggest, tau pathology starts in the entorhinal cortex and emanates from there,
the most effective approach may be to treat Alzheimer's the way we treat cancer
- through early detection and treatment, before it has a chance to
spread," study co-author Dr. Scott A. Small, professor of neurology at the
Columbia University Medical Center, said in the statement. "It is during
this early stage that the disease will be most amenable to treatment. That is
the exciting clinical promise down the road."
On the long run, the most breathless result from this work would be a
drug that could stop the tau contagion, much like an antibiotic or antiviral
are designed to thwart bacteria and viruses from their infectious mission. If
tau’s diseased form can jump from cell to cell, then blocking that infectious
leaping could put a halt to the slow cognitive decline that robs Alzheimer’s
patients of their minds, personality and lives.
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