Your Health ;
cautions that the leap from mice to men is a long
one and that Gandy’s experiments need to be dupli-
cated by other scientists in other labs before drug
companies invest billions of dollars to create new
medicines that target the oligomers.
Gandy’s new study looked at the most basic sci-
ence of the disease in a very di;erent way.
“Alzheimer’s seems to be caused by the buildup in
the brain of clumps of material that are formed by
the breakdown of protein,” Gandy says.
He now thinks the oligomers, not plaques, cause
the loss of memory and reason that characterize
Alzheimer’s. Gandy and colleagues published their
work in the Annals of Neurology in April.
Dillin, of the Salk Institute, started pursuing the
oligomer theory several years ago. Then, the idea
was so controversial, Dillin says, that some scien-
tists would walk out of the room when he made his
presentation at conferences. Now, he says, many of
the top researchers in the field are convinced.
protein breaks down naturally throughout our lives.
Tanzi and others suspect that as the body ages, too
many of these protein clumps create a damaging
buildup in the brain. They also may trigger the cre-
ation of tau tangles that further gum up the brain’s
signaling system.
The brain may try to remove the o;ending oligo-
mers by forming plaques. Tanzi goes so far as to call
the much-vilified plaques “brain pearls.” He says
that just as an oyster creates a pearl around a grain
of sand to protect itself, plaques may serve as traps
for the oligomers that are attacking the brain.
Researchers have found that some people who
never had dementia nevertheless have brains in-
undated with plaques. It may be, they theorize, that
their brains were exceptionally good at converting
the o;ending “sand” into “pearls.”
However, Tanzi adds, “plaques are not perfectly
safe.”
Compelling experiment
Alzheimer’s disease is characterized by two main
elements—the sticky plaques that form outside the
brain cells, and tangles of another protein, tau, that
twist around the inside of the cells. Both are thought
to play a role in the progression of the disease.
Scientists noticed the buildup of the sticky plaques
in the brains of people with Alzheimer’s disease
100 years ago. And although there has been some
debate, the prevailing science has held that sticky
plaques and tau tangles cause the damage.
Then, in 2004, scientists described mice that had
no plaque but nevertheless showed signs of demen-
tia. Other scientists showed that injecting rats with
the oligomers caused memory loss. Another lab
conducted an experiment to turn oligomers into
sticky plaques—they’re made of the same protein—
and “when they did this gene trick, the mice got
better, their memory improved,” Gandy says.
So Gandy and his colleague Michelle Ehrlich,
M.D., also a professor at Mount Sinai, genetically
engineered a new type of mice whose brains pro-
duce only oligomers but never brain plaques.
“Sam has done the most elegant experiments that
really put the nail in the co;n” of the older, more
widely accepted plaque theories, says Dillin.
Oligomers “should be enemy number one,” says
Rudolph Tanzi, director of the Genetics and Aging
Research Unit at Massachusetts General Hospital.
Tanzi calls the
much-vilified
plaques ‘brain
pearls.’ He
says just as an
oyster creates
a pearl around
a grain of sand
to protect
itself, plaques
may serve as
traps for the
oligomers that
are attacking
the brain.
Sticky plaques (pictured
above) are a hallmark of Alz-
heimer’s disease. But what
role do they play?
COURTESY ALZHEIMER’S ASSOCIATION
Targeting the right enemy
All this may help explain why research published
recently in the British journal the Lancet found even
though the new drug bapineuzumab reduced plaque
in the brain, study subjects failed to improve.
“I think the plaques are a sign that your brain was
trying to do something very beneficial for itself in
the last stages of the disease,” says Dillin. “If you go
in and take these plaques apart, you’re going to make
oligomers, and that could actually be worse.”
On the other hand, Dillin and others say, too much
protective plaque buildup in the brain may in fact
interfere with brain function.
Tanzi says he suspects the drugs that will work to
prevent Alzheimer’s or at least stop its progression
will not entirely destroy the oligomers—he thinks
the protein plays an important role in the brain—
but will limit their production. “Don’t expect to hit
it with a sledgehammer and still have the brain be
OK,” Tanzi says.
Several drugs in early stages of development are
aimed at oligomer production—including one Tanzi
is working on—but he says it will be at least a year
before we can expect to see results. Both his work
and Gandy’s are partially funded by the Cure Alz-
heimer’s Fund.
“The best drugs are yet to come,” Tanzi says. He
compares the first Alzheimer’s drugs to a 10-year-
old shooting a soccerball from midfield. “Now
we’ve got a division-one college team driving down
the field.” ;
Plaques as pearls
The plaques and oligomers are originally formed
from a protein found in the body. This amyloid
Elizabeth Agnvall is a contributing editor at the
AARP Bulletin.
