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Researchers Find Natural Defense to Fight
Alzheimer's Disease
Feb. 16, 2006 – Canadian scientist say they have
made a significant discovery that could be an important step towards a
new therapeutic approach to Alzheimer's disease. They have demonstrated
that bone marrow-derived microglia infiltrate amyloid plaques that cause
AD and succeed in destroying them "most efficiently" in mice.
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A team from the Faculty of Medicine at Université
Laval and the research centre at CHUQ (Centre Hospitalier Universitaire
de Québec) has discovered a natural defense mechanism that the body
deploys to combat nerve cell degeneration observed in persons with
Alzheimer's disease (AD).
Investigators Alain R. Simard, Denis Soulet,
Genevieve Gowing, Jean-Pierre Julien and Serge Rivest describe this
major discovery in the today's issue of the scientific journal Neuron.
Alzheimer's disease is characterized by the
accumulation of amyloid proteins in the brain. These proteins form
plaques around which microglia, the central nervous system's immune
cells, aggregate. These microglia appear to be incapable of eliminating
the plaques, and this has led some researchers to postulate that
microglial action produces an inflammation causing neuronal death. The
fact that Alzheimer's patients are prescribed anti-inflammatory drugs
results from this concept of the disease.
For Serge Rivest and his team, whose research is
funded by the Canadian Institutes of Health Research (CIHR), microglia
are not part of the problem, but of its solution. These investigators
have observed that, although the brain's resident microglia do appear to
be poorly equipped for combating amyloid plaques, an entirely different
case prevails for another type of microglia: those derived from bone
marrow stem cells.
Using tests conducted with transgenic mouse models
of AD, the investigators have demonstrated that bone marrow-derived
microglia infiltrate amyloid plaques and succeed in destroying them most
efficiently. These newly-recruited immune cells are specifically
attracted by the amyloid proteins that are the most toxic to nerve
cells.
"The discovery made by Dr. Rivest and his team is
an important step towards a new therapeutic approach to Alzheimer's
disease," states Dr. Rémi Quirion, Scientific Director of the Institute
of Neurosciences, Mental Health and Addiction (INMHA). "It is the
perfect example of the potential social benefits of investing in health
research."
According to Dr. Rivest, anti-inflammatory drugs
should not be administered in cases of Alzheimer's disease, as they
interfere with this natural defense mechanism. On the contrary, he adds,
a way must be found to stimulate the recruitment of a greater number of
bone marrow-derived microglia.
"Statistics show that 280,000 Canadians aged 65 and
over have Alzheimer's," says Anne Martin-Matthews, Scientific Director
of the CIHR Institute of Aging (IA). "This project gives hope to
seniors, families and caregivers who are concerned by this disease. It
illustrates the role health research can play in improving the health of
Canadians."
Dr. Serge Rivest's team also had recourse to
genetic engineering, in order to manufacture microglia that can anchor
themselves more solidly to plaques and that are equipped with enzymes
with more efficient plaque-destroying capability.
"Stem cells should be harvested from the patients
themselves, thus limiting the risks of both rejection and adverse
effects," says Dr. Rivest. "While this cellular therapy will not prevent
Alzheimer's, by curbing plaque development, we believe that it will help
patients prolong their autonomy and cognitive capacity. We believe that
this is new and powerful weapon in the fight to conquer Alzheimer's."
About CIHR
The
Canadian Institutes of Health Research (CIHR) is the Government of
Canada's agency for health research. CIHR's mission is to create new
scientific knowledge and to catalyze its translation into improved
health, more effective health services and products, and a strengthened
Canadian health care system. Composed of 13 Institutes, CIHR provides
leadership and support to close to 10,000 health researchers and
trainees across Canada.
http://www.cihr-irsc.gc.ca/
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