Alzheimer's, Dementia & Mental Health
Alzheimer’s Cause May be Amyloid Oligomers Rather
Than Amyloid Plaques
Memory problems originate with protein clumps
floating in the brain, says new research
April 29, 2010 - Using a new mouse model of
Alzheimer's disease, researchers at Mount Sinai School of Medicine
report to have
found that Alzheimer's pathology originates in Amyloid-Beta (Abeta)
oligomers in the brain, rather than the amyloid plaques previously
thought by many researchers to cause the disease.
The study, which was supported by the "Oligomer
Research Consortium" of the Cure Alzheimer Fund and a MERIT Award from
the Veterans Administration, appears in the journal Annals of
Neurology.
"The buildup of amyloid plaques was described over
100 years ago and has received the bulk of the attention in Alzheimer's
pathology," said lead author Sam Gandy, MD, PhD, Professor of Neurology
and Psychiatry, and Associate Director of the Alzheimer's Disease
Research Center, Mount Sinai School of Medicine.
"But there has been a longstanding debate over
whether plaques are toxic, protective, or inert."
Several research groups had previously proposed
that rather than plaques, floating clumps of amyloid (called oligomers)
are the key components that impede brain cell function in Alzheimer's
patients. To study this, the Mount Sinai team developed a mouse that
forms only these oligomers, and never any plaques, throughout their
lives.
The researchers found that the mice that never
develop plaques were just as impaired by the disease as mice with both
plaques and oligomers. Moreover, when a gene that converted oligomers
into plaques was added to the mice, the mice were no more impaired than
they had been before.
"These findings may enable the development of
neuroimaging agents and drugs that visualize or detoxify oligomers,"
said Dr. Gandy.
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New Test to
Detect Alzheimer’s Early Does It by Measuring A-Beta Oligomers
A new test
developed by Japanese scientists may revolutionize how and when
physicians diagnose Alzheimer's disease. According to research
in The FASEB Journal, the new test measures proteins in
the spinal fluid known to be one of the main causes of brain
degeneration and memory impairment in Alzheimer's patients -
high molecular weight A-Beta oligomers.
This tool,
once fully implemented, would allow physicians to diagnose and
treat Alzheimer's disease in its early stages, a time when
diagnosing the disease is very difficult.
Scientists
developed a tool to specifically measures A-Beta oligomers. They
then compared the levels of these protein aggregates in human
cerebrospinal fluid samples among three groups of people:
1) patients with diagnosed Alzheimer's disease;
2) patients with mild cognitive impairment who went on to
develop Alzheimer's disease; and
3) a control group with no symptoms of Alzheimer's disease.
Results
showed that the levels of the a fragments being measured
directly correlated to the extent of memory impairment, with the
highest levels found in those with confirmed Alzheimer's and
intermediate levels in those with mild cognitive impairment.
This shows that by measuring the levels of A-Beta oligomers in
cerebrospinal fluid, physicians may be able to identify
Alzheimer's disease before it can be clinically diagnosed using
current methods.
"Alzheimer's disease is a growing problem, due to aging of the
population in all developed countries," said Takahiko Tokuda,
M.D., Ph.D., a researcher from the Department of Neurology at
the Kyoto Prefectural University of Medicine Graduate School of
Medical Science in Japan who was involved in the work. "We hope
that our new diagnostic test will, in the future, significantly
improve the lives of people with Alzheimer's disease, and lead
to much better ways of treating this devastating disorder."
"Baby
boomers are getting older and Alzheimer's disease will have a
tremendous impact on the memory of a generation and the lives of
its children," said Gerald Weissmann, M.D., Editor-in-Chief of
The FASEB Journal. "This test is not only useful for the early
detection of Alzheimer's disease, but promises to be a marker
for the efficacy of newer treatments that are already on the
drawing board."
>>
The FASEB Journal |
"New neuroimaging agents that could monitor changes in
Abeta oligomer presence would be a major advance. Innovative
neuroimaging agents that will allow visualization of brain oligomer
accumulation, in tandem with careful clinical observations, could lead
to breakthroughs in managing, slowing, stopping or even preventing
Alzheimer's.
"This is especially important in light of research
reported in March showing that 70 weeks of infusion of the Abeta
immunotherapeutic Bapineuzumab® cleared away 25 percent of the Abeta
plaque, yet no clinical benefit was evident."
The Mount Sinai research team included Michelle
Ehrlich, MD, Professor of Pediatrics, Neurology, and Genetics and
Genomic Sciences, and John Steele, a Mount Sinai graduate student, who
performed the key analyses of the behavioral data.
Dr. Charles Glabe, an
oligomer expert and a member of the Cure Alzheimer Fund research
consortium, is also a co-author of the paper. Dr Gandy is also a
neurologist at the James J Peters Veterans Affairs Medical Center, an
affiliate of Mount Sinai School of Medicine.
About Source: Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The
Mount Sinai Hospital and Mount Sinai School of Medicine. Established in
1968, Mount Sinai School of Medicine is one of few medical schools
embedded in a hospital in the United States. It has more than 3,400
faculty in 32 departments and 15 institutes, and ranks among the top 20
medical schools both in National Institute of Health funding and by U.S.
News & World Report.
The school received the 2009 Spencer Foreman Award
for Outstanding Community Service from the Association of American
Medical Colleges.
The Mount Sinai Hospital, founded in 1852, is a
1,171-bed tertiary- and quaternary-care teaching facility and one of the
nation's oldest, largest and most-respected voluntary hospitals. In
2009, U.S. News & World Report ranked The Mount Sinai Hospital among the
nation's top 20 hospitals based on reputation, patient safety, and other
patient-care factors. Nearly 60,000 people were treated at Mount Sinai
as inpatients last year, and approximately 530,000 outpatient visits
took place.
For more information, visit
www.mountsinai.org.
