2023-06-02 14:07:13
Researchers were able to show that defective myelin actively promotes disease-related changes in Alzheimer’s
Alzheimer’s disease is an irreversible form of dementia and is considered to be the most common neurodegenerative disease worldwide. The most important risk factor for this disease is age, although it is not yet clear why. It is known that the insulating layer around nerve cells in the brain, also known as myelin, degenerates with age. Researchers at the Max Planck Institute (MPI) for Multidisciplinary Natural Sciences in Göttingen have now been able to show that defective myelin actively promotes disease-related changes in Alzheimer’s. Slowing down the rate of age-related myelin damage could open up new ways of preventing or delaying the progression of Alzheimer’s disease in the future.
© Max Planck Institute for Multidisciplinary Natural Sciences Certain immune cells, the microglia (yellow), clear amyloid plaques (magenta) in the brain of a mouse with Alzheimer’s disease (left). Degenerating myelin distracts them from it (right). © Max Planck Institute for Multidisciplinary Natural Sciences
What was I about to do? Where did I put the key? When was the appointment again? It begins with slight memory lapses, then increasing problems follow, to orientate oneself, to follow conversations, to express oneself, to make simple movements. In the last phase, those affected are usually in need of care. Alzheimer’s disease is insidious and mostly affects older people. The risk of developing Alzheimer’s doubles every five years from the age of 65
signs of aging in the brain
“The basic mechanisms for the connection between old age and Alzheimer’s have not yet been elucidated,” explains Klaus-Armin Nave, Director at the MPI for Multidisciplinary Natural Sciences. with his department Neurogenetik he researches the function of the myelin, the fat-rich insulating layer of the nerve fibers of nerve cells running in the brain. Myelin ensures fast communication between nerve cells and supports their metabolism. “Intact myelin is crucial for normal brain function. We were able to show that age-related changes in myelin promote pathological changes in Alzheimer’s disease,” continues Nave.
In a new study, which has now been published in the scientific journal Nature, the researchers investigated the possible role of age-related myelin degradation in the development of Alzheimer’s. Her work focused on a typical feature of dementia: “Characteristic of Alzheimer’s are the deposits of certain proteins in the brain, the so-called amyloid beta peptides or Aꞵ peptides for short,” explains Constanze Depp, one of the two first authors of the study. “The Aꞵ peptides clump together to form amyloid plaques. In those affected, these plaques form many years and even decades before the first symptoms of Alzheimer’s appear.” During the course of the disease, nerve cells eventually die irreversibly and the transmission of information in the brain is disrupted.
Using imaging and biochemical methods, the researchers examined and compared various mouse models of Alzheimer’s disease, in which amyloid plaques occur similar to those in Alzheimer’s patients. For the first time, however, they examined Alzheimer’s mice, which also had myelin defects, such as those that also occur in the human brain with advanced age.
Ting Sun, the second first author of the study, describes the results: “We have seen that myelin degradation accelerates the deposition of amyloid plaques in the brains of Alzheimer’s mouse models. The defective myelin puts a strain on the nerve fibers, causing them to swell and produce more Aꞵ peptides.”
Overwhelmed immune cells
At the same time, the myelin defects attract the attention of the brain’s immune cells, the microglia. “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,” says Depp. Normally, the microglia recognize and clear amyloid plaques, keeping the deposits in check. However, when the microglia are confronted with both defective myelin and amyloid plaques, they primarily remove the remnants of myelin while allowing the plaques to continue to accumulate. The researchers suspect that the microglia are ‘distracted’ or overwhelmed by the myelin damage and are therefore unable to react properly to plaques.
The results of the study show for the first time that defective myelin in the aging brain increases the risk of depositing Aꞵ peptides. “We hope that this will also lead to new therapies. If it were possible to slow down age-related myelin damage, this could also prevent or slow down Alzheimer’s disease,” explains Nave.
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