Sept. 15--Millions of dollars are going to studies that could point to possible
ways of preventing Alzheimer's disease by blocking the buildup of a certain
protein in the brain.
George Perry, dean of the College of Sciences at the University of Texas at San
Antonio, doesn't think the effort will work.
"You're not going to have a benefit," he said.
Perry is a prominent skeptic of a popular belief among many Alzheimer's experts
that the accumulation in the brain of a type of amyloid protein could be the
root of the disease.
Other researchers attribute the cause to the protein tau, which also has been
identified in brains that have suffered repeated injuries.
Perry, whose academic background is in marine biology, rejects that protein
formations cause Alzheimer's, going so far as to call the approach simplistic
and na ve.
Instead, Perry thinks the answer lies in the problems that can emerge in cell
energy production and in what's known as oxidative damage or oxidative stress.
Cells create energy through metabolism, but the process also generates
byproducts called free radicals that can damage the cell. The body has various
ways of neutralizing free radicals, but evidence suggests the damage can
snowball over time, contributing to aging and age-related diseases.
Perry, editor-in-chief of the Journal of Alzheimer's Disease, does not say that
oxidative damage definitively causes the disease, and even if it does, he's not
exactly sure how. He points out that many factors play a role -- genetics, for
example, partly dictate at what age someone develops Alzheimer's.
But, he said, oxidative damage appears early, perhaps marking the transition
between normalcy and illness.
Veronica Galvan, an assistant professor who studies Alzheimer's at the Barshop
Institute for Longevity and Aging Studies in San Antonio, said she thinks
amyloid has at least some sort of causative role in the disease.
She said debates such as these are a part of science.
Perry "has an alternative interpretation of the data," Galvan said.
The protein approach is, in many ways, a more hopeful one. If scientists can
find ways to preclude the protein buildup, then they possibly could find ways to
prevent the disease. But if oxidative stress is the underlying root of the
disease, then essentially everyone is vulnerable if they live long enough.
"That's why this idea of the amyloid cascade is so appealing," Perry said. "If
you stop the cascade, then people would be set free."
Perry does not discount the presence of protein in the brains of people with
Alzheimer's. Instead of viewing them as the cause, however, he thinks the
amyloid formations -- or plaques -- may be a result of the disease. There also
are people who have brains full of amyloid who remain cognitively sound into
"My theory is that oxidative stress is another part -- just like the amyloid is
a response to the disease," he said. "The fundamental problem relates to how the
brain deals with energetics. And I don't completely know how it works."
Perry is one of many scientists challenging the ideas focused on proteins, said
Maria Carrillo, vice president of medical and scientific relations at the
Alzheimer's Association, which has funded some of Perry's research.
Carrillo said there are about six mainstream hypotheses for the cause of
Alzheimer's. So many clinical trials look at amyloid because it was the first
potential cause linked to the disease, she said. But as the other hypotheses
have advanced, experts have been working to develop therapeutic approaches based
on those ideas.
"We don't want to put all our eggs in one basket," Carrillo said.
The problem with any Alzheimer's theory -- whether the amyloid premise or
Perry's hypothesis -- is that studies so far have failed to provide conclusive
evidence of disease causation, experts said.
"There are several reasons to think that certain forms of amyloid may play an
early role in the development of Alzheimer's disease, and there are several
reasons to temper that enthusiasm," said Dr. Eric Reiman, executive director of
the Banner Alzheimer's Institute in Arizona, who's working on a study aimed at
finding an improved test of the amyloid hypothesis.
At the same time, better evidence is also required to make other hypotheses like
Perry's more compelling, Reiman said.
First, sea urchins
Perry, who grew up in California, entered college knowing he wanted to be a
scientist, but thought his future would be in marine biology studying
"I wasn't interested in anything with a backbone," he said.
A zoology major in his undergraduate years, Perry earned his doctorate in marine
biology, writing about oxidative stress in sea urchin fertilization. More
broadly, he was interested in comparative biochemistry, examining how organisms
adapt to their environment.
After a post-doctoral fellowship at the Baylor College of Medicine, it was time
for him to find a faculty position. There were few marine biology positions
available, but Case Western Reserve University in Cleveland had a spot open for
someone to study Alzheimer's.
In other words, Perry fell into the field.
"I had never heard of the disease," he said.
David Epel, a professor emeritus of biology at Stanford who was Perry's graduate
adviser, said Perry's current research is not as far away from his academic
training as it might appear.
"There's actually a remarkable continuity between his original thesis and what
he does today," Epel said. "He started out with the production of free radicals
at the beginning of life, and now he's looking at it at the end of life."
His background -- focused on organisms adapting to conditions also informs how
Perry approaches Alzheimer's.
He said he thinks about how the disease fits into normal processes like aging
and how outside issues, including diet and exercise, relate to the development
or the postponement of the disease.
Perry came to UTSA from Case Western in 2006 and said most of his attention is
dedicated to administrative work at a time when the university is trying to
enhance its research profile. But he said his duties as dean have helped boost
his research, saying he's more productive when juggling different jobs.
Perry said his ideas about Alzheimer's are rejected by some scientists and that
he has been turned down for grants because of them.
However, being a leading and vocal skeptic has helped him in other ways. He's
well-known and published frequently, as his 135-page resume attests.
Some of his articles have invoked great historical challenges to accepted
beliefs as they questioned the protein ideas. In 2001, for example, Perry
co-authored a review article that dubbed the protein school of thought the
"Church of the Holy Amyloid." The article's title was "Copernicus Revisited."
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