Alzheimer’s disease is a progressive brain disorder that affects memory, thinking, and behavior. It is the most common cause of dementia in the elderly and is characterized by loss of brain cells and shrinkage of brain tissue. According to the World Health Organization, Alzheimer’s disease affects about 50 million people worldwide, and this number is expected to triple by 2050.
Researchers at the German Center for Neurodegenerative Diseases (DZNE)
Alzheimer’s disease
Alzheimer’s disease is a disease that attacks the brain and causes mental decline that worsens over time. It is the most common form of dementia, accounting for 60-80% of dementia cases. There is currently no cure for Alzheimer’s disease, but there are medications that can help relieve symptoms.
”data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]≫Patients with Alzheimer’s disease.Their findings were recently published in a prestigious journal Nature.
“Although medin has been known for over 20 years, its impact on disease was previously underestimated. ,” says Dr. Jonas Neher of DZNE’s Tübingen site, who led the study.
The Harty Institute for Clinical Brain Research in Tübingen, the University of Tübingen, and various international institutions and partners were also involved in this long-term project.
Medin belongs to the group of amyloids. Of these proteins, amyloid-β is best known because it aggregates in the brains of Alzheimer’s disease patients. These aggregates not only deposit directly in brain tissue as so-called plaques, but also in their blood vessels, damaging nerve cells and blood vessels, respectively. However, while many studies have focused on amyloid-β, medin has not been the focus of interest. Very few were, and this is often a prerequisite for more in-depth studies of amyloid,” explains Jonas Neher.
However, Mezin is actually found in almost all blood vessels over the age of 50, making it the most common amyloid known. Jonas Neher and his team first discovered that medin also occurs in aged mice, a finding he reported two years ago in the scientific journal PNAS. It was found at the time that the older the mouse, the more medin accumulates in the blood vessels of the brain. However, this ability to dilate blood vessels is important for the optimal supply of oxygen and nutrients to the brain.
For their latest results, the researchers built on this foundation and focused specifically on Alzheimer’s disease. could be shown to accumulate more strongly in blood vessels in the brain. Importantly, these findings were confirmed when brain tissue from organ donors with Alzheimer’s disease was analyzed. However, when mice were genetically engineered to prevent medin formation, they developed significantly less amyloid-β deposits, resulting in less damage to blood vessels.
“There are only a handful of research groups in the world working on Medinin,” says Jonas Neher. Most recently, a US study reported that levels of mezin may be elevated in patients with Alzheimer’s disease. remained.
“Now, through a number of experiments, we have been able to show that medin does promote vascular pathology in Alzheimer’s disease models,” said Neher. So medin deposits are indeed the cause of vascular damage.”This shows that medin is one of the causes of the disease,” he said.
In their study, the researchers stained tissue sections from both mice and Alzheimer’s patients to see specific proteins. This allowed us to show that medin and amyloid-β co-deposit in blood vessels in the brain – co-localization is the technical term for this. We were able to prove that it does, that is, it forms mixed deposits.
“Surprisingly, medin directly interacts with amyloid-β and promotes its aggregation, which was completely unknown,” Jonas Neher summarizes the results.
Precisely from this insight, researchers see hope in the development of new treatments. “Medin may be a therapeutic target to prevent vascular damage and cognitive decline due to amyloid accumulation in blood vessels in the brain,” they conclude. It is uncontroversial among experts that, in addition to amyloid-β aggregates in brain tissue, the development of Alzheimer’s disease is also facilitated by vascular alterations, ie, decreased function and damage to blood vessels. Therefore, treatments that target affected blood vessels, not just plaque, may help patients.
Next, we need to determine whether medin aggregates can be removed therapeutically and whether this intervention actually affects cognitive performance. I’m here. This is because they are a very good reflection of the pathological changes in Alzheimer’s patients.
See also: “Medin and Vascular Amyloid-β Coaggregation in Alzheimer’s Disease” Jessica Wagner, Caroline Degenhardt, Marlene Bate, Nikolaos Roulos, Caterina Constanturea, Angelos Skodoras, Catherine Wilde, Ping Liu, Ulrike Obermuller, Vikas Bansal, Anupriya Dalmia , Tammaryn Lashley, Thomas Deller, Marla Gearing, Lary C. Walker, Peter Heutink, Frederic Rousseau, Joost Schymkowitz, Mathias Jucker, Jonas J. Neher, 16 November 2022, Nature.
DOI: 10.1038/s41586-022-05440-3
