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 defence 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 February 16th 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 defence 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."
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