2023-06-05 09:49:54
A new starting point in the fight against Alzheimer’s dementia is emerging: neuroscientists have discovered a role for the insulating layer of nerves in the disease: the age-related breakdown of this so-called myelin promotes the formation of amyloid plaques, studies on the mouse model show. Slowing myelin degeneration may therefore make it possible to delay the progression of Alzheimer’s disease, the researchers say.
Everyone forgets something from time to time and it is also normal that some cognitive performance decreases with age. But for millions of people, this is taking on dramatic proportions: Alzheimer’s disease is considered the world’s most common form of neurodegenerative dementia. The risk of developing the disease is clearly linked to age – from the age of 65 it doubles every five years. The development of Alzheimer’s occurs gradually: For example, at the beginning those affected forget their keys more and more often – but in the advanced stage they often no longer understand their function. This then usually requires intensive care. Due to the enormous medical and social importance, the causes, development processes and thus possible starting points for the treatment of Alzheimer’s are being intensively researched. But there are still many open questions.
Brittle myelin in sight
“Above all, the basic mechanisms for the connection between old age and Alzheimer’s are still unclear,” says senior author Klaus-Armin Nave from the Max Planck Institute for Multidisciplinary Natural Sciences (MPI-NAT) in Göttingen. It is clear that certain deposits in the nerve cells of the brain are at the root of the functional disorders: so-called amyloid beta peptides clump together over the course of the disease to form plaques, which ultimately lead to the death of nerves. As part of the study, the international research team has now followed up indications that an already prominent component of nerve cells could be involved in the process: the myelin. This is the fat-rich insulating layer of the nerve fibers running in the brain, which, in addition to other functions, above all ensures undisturbed transmission of stimuli.
The myelin is known for its role in multiple sclerosis: In this autoimmune disease, this substance is attacked, resulting in neuronal disorders. It is also already known that the myelin layer degenerates with age – it becomes thinner and more brittle. As part of their study, the researchers have now explored whether this change could be linked to the development of Alzheimer’s. To do this, they carried out studies on “Alzheimer mice”. These are certain cultivated forms of the rodents that form amyloid plaques in the brain in a similar way to Alzheimer’s patients. For the first time, however, the team examined Alzheimer’s mice, which also had myelin defects, such as those that also occur in the human brain with advanced age.
Swollen nerve fibers and overwhelmed immune cells
As the scientists report, they have now been able to demonstrate clear connections between the two aspects with the help of imaging and biochemical examination methods: “We found that myelin degradation accelerates the deposition of amyloid plaques in the brain of Alzheimer’s mouse models,” summarizes Co-Erst -Author Ting Sun from MPI-NAT. In concrete terms, it was first shown that the defective myelin is linked to stress on the nerve fibers, which leads to swelling and increased formation of amyloid beta peptides. The results of the study also showed that the myelin defects attract the attention of the brain’s immune cells – the microglia – and thus contribute to plaque formation.
“These cells are very alert and monitor the brain for any sign of impairment. They can absorb and destroy substances such as dead cells or cell components,” explains co-first author Constanze Depp from the MPI-NAT. Normally, the microglia recognize and clear amyloid plaques, providing a garbage disposal effect. However, the observations now show that when the microglia are confronted with both defective myelin and amyloid plaques, they primarily remove the myelin remnants. The plaques, on the other hand, can continue to accumulate. The researchers explain that the microglia are probably distracted by the myelin damage or are overwhelmed with the clean-up effort.
At least in the mouse model, it is becoming apparent that age-related changes in the myelin promote the pathological changes in Alzheimer’s disease. According to the team, this finding could have great potential: “If the results can be confirmed in humans, the promotion of myelin health should be considered as a therapeutic goal,” the scientists write. Nave concludes: “If it were possible to slow down age-related myelin damage, this could also prevent or slow down the onset of Alzheimer’s disease,” says the neuroscientist.
Source: Max Planck Institute for Multidisciplinary Natural Sciences, Article: Nature, doi: 10.1038/s41586-023-06120-6
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