21 September 2015

The development of Alzheimer's disease is facilitated by a violation of the BBB

Doctors: brainwashing can cure people of Alzheimer's disease

One of the reasons for the development of Alzheimer's disease may be the blocking of special ducts in the vessels of the brain through which protein "garbage" is excreted, and their re-opening and "washing" of the brain can save patients from this disease, Irish doctors write in the journal Science Advances (Keaney et al., Autoregulated paracellular clearance of amyloid-β across the blood-brain).

It is believed that Alzheimer's disease is caused by the accumulation of a pathogenic substance inside neurons, the beta-amyloid protein. It is formed from the "scraps" of the APP protein, which is involved in the processes of repairing damaged neurons and forming connections between them. Violations in the processing of molecules of this protein lead to the appearance of beta-amyloid plaques and the destruction of nerve cells. Recently, scientists have found out that Alzheimer's disease can be contagious (: see the article "False sensation in the wake of one discovery" – VM :).

James Keaney from Trinity College in Dublin (Ireland) and his colleagues found another potential cause of this disease and a way to treat it by studying the structure of the brain and its environment in the heads of several people who died from Alzheimer's disease, as well as conducting experiments on rodents.

Our brain is isolated from the rest of the body by the so–called blood-brain barrier (BBB) - a dense layer of special astrocyte cells surrounding all the blood vessels of the brain and not letting anything inside it except oxygen and nutrients.

As scientists explain, this barrier is not a monolithic wall, but a set of peculiar cells-"bricks", between which there are small ducts, the so-called "tight contacts". They are the walls of two neighboring cells, cross–linked to each other by molecules of two special proteins - claudins and occludins.

In a normal state, these ducts are blocked, and even the smallest molecules cannot penetrate through them, but they can be opened if necessary. As shown by experiments that Kini and his colleagues conducted on mice, these channels play an important role in the fight of brain cells with beta-amyloid.

For example, when scientists injected a solution of this protein into the brains of healthy rodents, the width of "tight contacts" increased, which allowed protein plaques to leave the brain and go into the circulatory system, where they were destroyed by immune cells.

This was due to the fact that the presence of "scraps" of APP protein caused the cells of the blood-brain barrier to stop producing molecules of claudines and occludines, as a result of which the channels opened and began to release large particles of "protein debris" from the nerve tissues.

In the inset, white lines show proteins that seal tight contacts between endothelial cells.
Figure from the note Helping Clear Out Amyloid-β in Chemical & Engineering News – VM.

Such "brainwashing" apparently does not occur in the vessels of mice and people suffering from Alzheimer's disease, as a result of which beta-amyloid begins to gradually accumulate in the nervous tissue and destroy neurons, gradually depriving a person of memory and life.

This brain self-cleaning system, scientists hope, can in principle be used to "push" antibodies that neutralize beta-amyloid plaques through the BBB, which will allow them to clean the brain of patients from protein debris. In addition, the forced activation of these channels by itself can help people suffering from Alzheimer's disease, or completely get rid of it, or slow down the course of its development, scientists conclude.

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