Every two weeks, a researcher from the Collège de France discusses a topical scientific issue.
Alzheimer's disease affects nearly 55 million people million people worldwide, with no hope of a cure for lack of treatment. Ongoing research into the drainage mechanism of toxic substances at the root of the disease is raising hopes of improved care for sufferers.
Interview with Marie Karam*, biologist at the Collège de France.
Alzheimer's disease is neurodegenerative. It causes progressive, irreversible deterioration of the neurons. This deterioration leads to difficulties in memorizing, speaking and moving, culminating in loss of autonomy and death. The causes of this deterioration are poorly understood. Biologist Marie Karam explains that " new leads suggest that disruption of the drainage of toxic substances from the brain could be a cause of the disease, or at the very least an aggravating factor. "
In this disease, toxic proteins are responsible for the degeneration of neurons, mainly amyloid proteins. Amyloid beta, naturally present in the brain, sometimes accumulates abnormally, forming toxic plaques known as amyloid plaques. The origin of this accumulation is thought to lie in a genetic mutation. We know that amyloid plaques play a crucial role in neuronal degradation," continues Marie Karam. Their presence generates a deposit of toxic products in the brain. It is possible that, in a sort of vicious circle, these products disrupt the brain's drainage mechanism and contribute to the increased formation of amyloid plaques. "
Cleansing the brain
Cerebral drainage relies on the cerebrospinal fluid in which the brain is immersed. This fluid transports waste and pathogens outwards for elimination. Amyloid plaques disrupt the function of small immune cells, called macrophages, found between brain tissue and blood vessels. These cells are responsible for cleaning up brain waste carried by the cerebrospinal fluid. Marie Karam explains :" It appears that the failure of macrophages accelerates the accumulation of the protein at the origin of plaques : the cycle is self-perpetuating. As these plaques also create inflammatory reactions, they exacerbate the symptoms of Alzheimer's disease. "
The study of brain drainage is a new way of understanding Alzheimer's disease. Researchers only became interested in this phenomenon in 2012." Since then, many teams, including ours, have been exploring this avenue. I first noticed the absence of lymphatic vessels in the brain. If the brain didn't have the usual organ-cleansing system, how could it regulate itself ? We had to discover and then describe how this mechanism worked. My work is now focused on understanding macrophage activity. "
Preventive approaches
The practical applications of this research are promising. The development of treatments to stimulate macrophage activity and improve cerebrospinal fluid transport could facilitate the elimination of amyloid plaques, thereby slowing the progression of Alzheimer's disease." We can imagine treatments that would act before damage begins to appear on neurons. " These preventive approaches could focus on amyloid proteins, preventing them from clumping together and forming plaques." Improving the efficiency of brain drainage will enable the brain to get rid of proteins before plaques appear. We could break the vicious circle of accumulation before it starts. We would only be acting on one cause of the disease among others, but we believe this would considerably reduce its progression. "
In the absence of curative treatments, research into brain drainage and macrophages could profoundly alter our approach to Alzheimer's disease, offering unprecedented hope to sufferers and their families.
*Marie Karam is a researcher in the Molecular Control of Neurovascular Development team at the Collège de France's Interdisciplinary Biology Research Center, under the supervision of Dr. Isabelle Brunet.
