Medin: A key protein in age-related blood vessel changes and dementia

Medin is produced naturally in the human body. However, problems arise when it clumps together: this happens in the arteries, and when accumulations of the protein form there, the physical properties of the blood vessels change: they become stiffer, which in turn prevents the necessary regulation of blood flow. If this happens in the blood vessels of the brain, it has a direct impact on the nerve cells, which can no longer be adequately supplied. This makes medin a possible trigger for vascular dementia. However, restricted blood supply also plays a role in numerous other forms of dementia; Alzheimer's disease, for example, often has a vascular component. Whether and how medin is involved is currently the focus of research. 

Medin is closely related to another protein called MFGE8, which fulfils an important task in the body: once minor injuries occur in blood vessels, it contributes to healing processes there. When such injuries appear, the production of MFGE8 is automatically upregulated. After the work is done and the protein is broken down, medin is produced as a by-product of the breakdown. This natural process only becomes problematic when too much medin is deposited in the vessels.

It is clear that medin is associated with age. In plain language: the older a person gets, the more medin is present in the body – although the actual amount varies greatly from person to person. One hypothesis is that many microscopic injuries occur in the blood vessels over the course of a lifetime, resulting in the formation of a corresponding amount of MFGE8 over the years – and ultimately a lot of medin. This would explain why its concentration increases with age.

In addition to vascular stiffening, there is evidence of another consequence of medin accumulation: it apparently interacts with amyloid beta, the protein that accumulates in the brains of Alzheimer's patients. According to current knowledge, medin promotes the aggregation of amyloid beta, again particularly in blood vessels – this is a direct link to Alzheimer's dementia. 

Medin itself also belongs to the amyloid family. Amyloids are proteins that are folded in a specific way; currently, around three dozen different types of amyloid are known, some of which are associated with specific diseases. And just as amyloid beta is specific to brain diseases such as Alzheimer's, medin is specific to cardiovascular diseases. Whether it causes damage in the brain or other organs depends on where exactly in the body medin is deposited in the bloodstream – this is also currently being investigated in more detail. 

After medin was first identified in 1999, it was quickly forgotten because researchers were initially unable to establish a clear link to a specific disease. A study by the DZNE in 2022 proved that medin plays a role in Alzheimer's disease. Since then, various research teams have established new connections.

Researchers hope that medin can be used as a biomarker in the future: as an indicator of blood vessel diseases. Physicians currently have no way of detecting vascular pathology in dementia, i.e., damage to blood vessels in the brain. These are not visible in medical imaging techniques such as magnetic resonance imaging; so far, such changes can only be detected in a biopsy or by identifying damage to vessels that occurs very late in the disease. If medin could be measured in the nerve fluid (known as cerebrospinal fluid) and used to draw conclusions about the stage of a disease, this would be a major step forward. In a further step, a therapy targeting Medin could also be conceivable, which could be used to treat the vascular components of dementia. This is also currently being tested in model systems.