Until now considered the main cause of neurodegeneration in Alzheimer’s disease, beta-amyloid plaques could be formed as a defense by immune cells, reveals a new study.
- Contrary to the thesis so far adopted by the scientific world, the authors of this new study argue that beta-amyloid plaques are in fact a beneficial mechanism
- By organizing the diffuse plaque into dense core plaque, it thus helps to clear the debris present in the brain.
Are beta-amyloid plaques formed by immune cells present in our brain to protect neurons from cell death? This is the theory developed by a new study on Alzheimer’s disease, conducted by researchers at the Salk Institute for Biological Studies, located in San Diego (California).
A new theory about amyloid plaques
Until now, scientists attributed to these amyloid plaques the alteration of the mental functions of Alzheimer’s patients: by accumulating abnormally in the neurons, they gradually and irremediably caused brain damage. It is for this reason that current research is particularly focused on ways to reduce the buildup of these plaques.
In their study published in Nature Immunology, the researchers of the Salk Institute upset these certainties. Microglial cells, immune cells in the brain responsible for consuming debris such as beta-amyloid plaque that accumulate in the brains of patients, promote the formation of dense-core plaques, they say. This action would move the scattered plaques away from the neurons, and thus cause cell death.
“We show that dense-core plaques do not form spontaneously, explains Professor Greg Lemke, molecular neurobiologist at the Salk Institute. We think they’re built by microglia as a defense mechanism, so it’s best to leave them alone.” The researcher also believes that the treatments responsible for reducing this plaque with dense nuclei can “cause more damage”.
An “eat me” signal produced by dead cells
In Alzheimer’s disease, the two most common forms of plaque that form are “diffuse” and “dense-core.” Diffuse slabs are weakly organized amorphous clouds. Dense-core plates have a compact center surrounded by a halo. Scientists have generally thought that both types of plaques form spontaneously from excessive production of a molecule called amyloid precursor protein (APP).
However, the theory of this new study is that it is in fact microglial cells that form dense-core plaques from diffuse beta-amyloid fibrils, as part of their cellular cleansing.
This theory is based on a discovery made in 2016, which showed that when a brain cell dies, a fatty molecule moves from the inside to the outside of the cell, thus signaling “I’m dead, eat me “. Microglia, via surface proteins called TAM receptors, “eat up” the dead cell, with the help of an intermediary molecule called Gas6. Without TAM and Gas6 receptors, microglia cannot connect to dead cells and consume them.
This new work shows that amyloid plaques also diffuse the Gas6 molecule and the “eat me” signal. By conducting experiments in mice, the researchers showed that microglia with TAM receptors eat amyloid plaques via the “eat me” signal and Gas6. In mice engineered to lack TAM receptors, microglia were unable to perform this function.
A phenomenon to get rid of diffuse plaques
Digging deeper, the team discovered that after a microglial cell eats a diffuse plaque, it transfers the engulfed beta-amyloid to a very acidic compartment and transforms it into a very compact aggregate which is then transferred to a plaque. dense core. Researchers believe this is a beneficial mechanism, which organizes diffuse plaque into dense core plaque and rids the intercellular environment of debris.“Our research seems to show that when there are fewer dense-core plaques there seem to be more adverse effects”explains Professor Youtong Huang, first author of the article.
This discovery suggests new avenues of treatment for Alzheimer’s disease. It could also explain the failure of current treatments to destroy amyloid plaques in the brain. “We argue that beta-amyloid is still clearly a bad thing; it’s just that you have to wonder if dense-core plaques are really bad”concludes Professor Lemke.
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