Medin Amyloid May Be Important in Alzheimer's Disease

There are a score or so of proteins in the human body capable of producing amyloid when they misfold, by encouraging other molecules of the same protein to misfold in the same way, linking together to produce solid deposits in and around cells. Only those amyloids for which there is clear evidence of disease association or toxicity to cells have been well studied, unfortunately. That doesn't mean that the others are harmless! As demonstrated here, it may just be the case that researchers have to look a little harder to find the ways in which these amyloids are causing pathology in older people.

Medin belongs to the group of amyloids. Of these proteins, amyloid-β is best known because it clumps together in the brains of Alzheimer's patients. These aggregates then deposit both as so-called plaques directly in the brain tissue, but also in its blood vessels, thereby damaging the nerve cells and the blood vessels, respectively. But while many studies have focused on amyloid-β, medin has not been a focus of interest.

However, medin is actually found in the blood vessels of almost everybody over 50 years of age, making it the most common amyloid known. Medin even develops in aging mice. The older the mice get, the more medin accumulates in the blood vessels of their brains. What's more, when the brain becomes active and triggers an increase in blood supply, vessels with medin deposits expand more slowly than those without medin. This ability of blood vessels to expand, however, is important to optimally supply the brain with oxygen and nutrients.

Now researchers were able to show in Alzheimer's mouse models that medin accumulates even more strongly in the brain's blood vessels if amyloid-β deposits are also present. Importantly, these findings were confirmed when brain tissue from organ donors with Alzheimer's dementia was analysed. However, when mice were genetically modified to prevent medin formation, significantly fewer amyloid-β deposits developed, and as a result, less damage to blood vessels occurred. "There are only a handful of research groups worldwide working on medin at all. We have now been able to show through many experiments that medin actually promotes vascular pathology in Alzheimer's models, and this indicates that medin is one of the causes of the disease."



how feasible is a universal amyloid clearance therapy

Posted by: erasmus at November 23rd, 2022 6:16 AM
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