Transcription
[Music] Alzheimer's disease was described for the first time in 1907 by the German psychiatrist Alois Alzheimer. In performing a histopathologic study of the brain of his patient, Auguste D, suffering from dementia, he brought to light the presence of two types of lesions in the brain: amyloid plaques and neurofibrillary tangles. He reached the conclusion of a distinct disease of the cerebral cortex.
100 years later, thanks to current scientific techniques, research has made a great leap in the understanding of the disease. We know that the brain is made up of neurons and that these are interconnected to form a vast network. These connections, known as synapses, enable the transmission of information from one neuron to another. In Alzheimer's disease, 10 to 15 years before the appearance of the symptoms, two main lesions form in the brain: amyloid plaques composed of amyloid-beta protein and neurofibrillary tangles composed of tau protein.
[Music] How is the amyloid plaque formed? On the surface of the neuron is a large protein called APP. Normally, APP is sectioned by enzymes on the surface of the neuron, and it frees a protein called amyloid-beta. The amyloid-beta protein is then cleared in the body. In the case of Alzheimer's disease, there is an imbalance; the amyloid-beta protein is no longer regulated and is found in too great quantity. The proteins assemble to form insoluble fibrils and create amyloid plaques.
[Music] How are neurofibrillary tangles formed? When a neuron communicates with another, a signal goes from the body, known as the soma, to the synapse to transfer the information. The signal passes through the skeleton of the neuron composed of microtubules. These microtubules are stabilized by normal tau protein. In Alzheimer's disease, tau protein becomes defective and detaches from the microtubules; thus, the skeleton of the neuron dissociates as it is no longer maintained. Defective tau proteins then assemble to form filaments in the neuron. Without the skeleton, the neurons degenerate, and connections between the neurons are lost. The abnormal accumulation of tau filaments in the neuron creates neurofibrillary tangles and eventually causes the death of the neuron.
How do the two lesions spread throughout the [Music] brain? Neurofibrillary tangles and amyloid plaques do not follow the same pathway in the brain. Over time, neurofibrillary tangles first develop in the region called the hippocampus, which is essential to memory and learning. They then reach the whole brain following a centrifugal movement. The process causes atrophy, which engenders global dysfunction. The progression of the lesions corresponds with the symptoms of the disease, which begin with memory problems, followed by problems of language, recognition, and incapacity to perform gestures. Amyloid plaques develop differently. They are initially observed in the cortex, secondly in the hippocampus, and then the amyloid plaques reach the whole brain following a centripetal movement. Their progression does not correspond to the symptoms of the disease.
But numerous questions remain unanswered. We know that the presence of the two cerebral lesions is necessary to develop Alzheimer's disease, since one does not come without the other. But which lesion comes first, neurofibrillary tangle or amyloid plaque? The answer is still under debate. Many clinical trials destined to reduce amyloid plaques in the brain have failed. In fact, reducing them is not efficient to eradicate the disease. It has now been suggested that, well before formation of amyloid plaques, smaller forms of amyloid-beta, called oligomers, appear to be toxic for neurons, disturbing their communication when they fix onto synapses. It would appear that the toxic oligomers and their accumulation in amyloid plaques are at the origin of neurofibrillary tangles, which in their turn are responsible for symptoms.
The relationship between amyloid-beta protein and tau protein is still little understood. What is the exact sequence of molecular mechanisms leading to the development of dementia? What is the role of genetics and environmental risk factors in the appearance of the disease? Scientific research is essential in answering these questions. Thanks to researchers, Alzheimer's disease is better and better known in its complexity, and new avenues raise real hope for the eradication of this devastating disease.
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