Alzheimer's disease is complicated by poor pericyte function

Vascular problems increase Alzheimer's disease

Kirill Stasevich, CompulentaWith age, the brain begins to malfunction, and sometimes so much that a person is diagnosed with dementia.

But there are several age-related dementias, and they are characterized by the area of damage in the brain and the causes of occurrence.

One of the most common causes is Alzheimer's disease. It is believed that the disease is triggered by pathogenic forms of beta-amyloid and tau protein, which form insoluble deposits in neurons and cause their death; however, scientists are still arguing about the specific mechanism of the disease.

Another large-scale cause of age-related dementia is vascular in nature. Due to problems with blood vessels, some areas of the brain remain without blood supply, and hemorrhages occur in others. However, there is much more in common between vascular and alzheimeric dementia than it might seem. Firstly, patients with Alzheimer's syndrome often have problems with the vessels of the brain; secondly, the accumulation of beta-amyloid often occurs directly in the walls of blood vessels; thirdly, there is a commonality at the genetic level: the APOE4 gene, which is associated with alzheimer's, also affects the condition of blood vessels in the brain.

In addition, when experiments in mice tried to cause Alzheimer's disease by increasing the production of beta-amyloid in neurons, this led to the appearance of only individual signs of the disease. All this has led researchers to believe that dementia can be the sum of both alzheimer's and vascular factors, and without some vascular problems, Alzheimer's disease cannot enter full force.

According to scientists from the University of Southern California (USA), the unifying point here are pericytes – special cells surrounding the capillaries of the brain and controlling the exchange of molecules between blood and nervous tissue. It is believed that pericytes play a leading role in the blood-brain barrier, which protects the brain from unwanted "guests" traveling with blood. Interacting with other barrier cells, pericytes help to supply nerve cells with nutrients and remove metabolic products from them.

Blood vessels of the brain: the cells of the vessel wall are colored green,
the red dots highlight the associated pericytes. (Photo by wellcome images.)

To check whether pericytes are involved in Alzheimer's disease, Berislav Zlokovic and his collaborators created mice whose predisposition to the syndrome was combined with a reduced level of the platelet growth factor receptor. This protein, like other growth factors, manages cell division and differentiation, playing a particularly important role in the formation of blood vessels. Previous experiments have shown that the lack of receptors for this protein reduces the number of pericytes around the vessels, which worsens the functions of the blood-brain barrier.

It turned out, as the researchers write in Nature Communications (Sagare et al., Pericyte loss influences Alzheimer-like neurodegeneration in mice), that in mice with a normal predisposition to Alzheimer's disease and simultaneously suffering from a lack of pericytes, the symptoms of the disease went further: neurofibrillary tangles appeared in the hippocampus and cortex, and mass death of nerve cells occurred. cells. In animals that simply had increased beta-amyloid production, this either did not happen at all, or the symptoms did not manifest as much.

Further experiments have shown that without pericytes, beta-amyloid is retained in the nervous tissue. That is, a poorly functioning blood-brain barrier cannot remove harmful protein from the brain, which exacerbates the symptoms.

In addition, it turned out that the relationship between beta-amyloid and pericytes is mutual: the protein caused the death of pericytes and further worsened the condition of the blood-brain barrier. It turned out to be a vicious circle: the worse the pericytes worked, the more beta-amyloid remained in the nervous tissue, and the more of it remained, the worse the pericytes had.

That is, Alzheimer's disease, in order to unfold in full force, also needs bad blood vessels – or rather, a bad blood-brain barrier, which is not able to remove pathogenic protein debris from the brain.

In other words, the problem of Alzheimer's disease cannot be solved if the vessels of the brain are neglected. With age, the barrier between the brain and blood begins to work worse, so it would be worth thinking about how to restore its functionality, at least partially.

Prepared based on the materials of the University of Southern California:
USC study suggests brain blood vessels alter Alzheimer’s progression.

Portal "Eternal youth" http://vechnayamolodost.ru17.12.2013