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Discovery Could Lead to New Treatment for
Alzheimers
June 10, 2005 Researchers at UCLA think they have
made a discovery that may lead to a new approach in diagnosing and
treating Alzheimers Disease. They say the human body has its own
defense against brain aging - the immune system - which helps to clean
the brain of amyloid-beta waste products. They have discovered that some
patients with Alzheimer's disease have an immune defect making it
difficult to clean away these wastes. This may lead to over-saturation
of the brain with amyloid beta, which form amyloid plaques, the
definitive hallmark of Alzheimer's disease.
Published in today's issue of the Journal of
Alzheimer's Disease, the findings could lead to a new approach in
diagnosing and treating Alzheimer's disease by helping to diagnose and
correct this immune defect. This is the first time that researchers have
discovered that the innate -- or more primitive -- part of the immune
system may play a role in the development of Alzheimer's disease.
Using blood samples, investigators found that in
healthy people, cells belonging to the innate immune system called
macrophages, cleared amyloid-beta in a test tube test developed at UCLA.
However, the macrophages of some Alzheimer's patients could not
adequately perform this cleaning job.
"Macrophages are the janitors of the innate immune
system, gobbling up waste products in the brain and throughout the
body," said Dr. Milan Fiala, first author and UCLA researcher.
Fiala notes that there may be a problem either with
the macrophages not effectively binding to amyloid beta or a problem in
the absorption or uptake, which is called "phagocytosis." He adds that
this immune defect may also be present in other diseases where a
build-up of waste and plaques occur, such as in cardiovascular disease
and Gaucher's disease.
"If further study shows that this defective macrophage function is
present in most Alzheimer's disease patients, new hormonal or
immune-boosting approaches may offer new approaches to treating the
disease," adds Fiala.
Researchers add that this new approach differs from
the amyloid-beta immunization method, which utilizes another part of the
immune system called the adaptive immune system. According to Fiala, the
immunization approach has resulted in amyloid-beta clearance in the lab
in an animal model, but in a human clinical trial led to brain
inflammation in a subset of patients.
In future studies, investigators plan to regulate
the innate immune system by natural substances such as hormones, and
natural products such as curcumin (from the curry powder). Currently in
their lab, Fiala and Dr. George Bernard who is a professor in the UCLA
Department of Oral Biology and Medicine,are testing the effectiveness of
a naturally occurring hormone, called insulin-like growth factor I, in
conjunction with a research team from the MP Biomedicals LLC Company.
The study was funded by the Alzheimer's Disease
Association. The Sence Foundation and MP Biomedicals LLC Company are
supporting current studies involved in testing the effectiveness of
insulin-like growth factor I.
In addition, Fiala and MP Biomedicals LLC will also
be exploring the development of an in-vitro diagnostic test for early
detection of Alzheimer's disease.
Other investigators include: Dr. John Ringman, UCLA
Department of Neurology, and Dr. Francesco Chiappelli in the UCLA
Department of Oral Biology and Medicine.
The website to the Journal of Alzheimer's Disease
is
http://www.j-alz.com.
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