Russian scientists have discovered a possible “accelerator” of Alzheimer’s disease

Cholesterol may influence the formation of disease-associated amyloid plaques

A group of three Russian scientific organizations has discovered how cholesterol, an organic compound found in cell membranes, may be linked to the development of Alzheimer’s disease. Associate Professor of the Department of Physics of Living Systems at MIPT Oleg Batishchev spoke in more detail about the work of “MK”.

Scientists have long discovered a relationship between the development of senile neurodegenerative diseases and the presence of so-called amyloid plaques on the surface of neurons. These are deposits of the beta-amyloid protein in the gray matter of the brain that form on cell membranes. Now, for the first time, scientists have tested how other membrane components can influence their formation.

– Oleg, let’s sort it out in order. What kind of proteins are beta-amyloids and where do they come from?

– From their “healthy” precursors, which are initially present in neuronal cells and are responsible for our cognitive functions – memory, signal transmission in nerve cells, etc. There are certain enzymes that interact with them. Normally, this interaction is necessary for the functioning of the brain, but when some kind of disturbance occurs, be it a genetic mutation or hypoxia (oxygen starvation), it turns out that enzymes begin to cut off the “wrong pieces” from beta-amyloid precursors. Over time, these pieces turn into plaques, which most scientists associate with Alzheimer’s disease.

– And what new did your group find out?

– Employees of the Institute of Physical Chemistry and Electrochemistry named after. A. N. Frumkin RAS, Institute of Bioorganic Chemistry named after. M. M. Shemyakin and Yu. A. Ovchinnikov and the Moscow Institute of Physics and Technology for the first time studied the effect of other components of the neuronal cell membrane on the beta-amyloid precursor protein. First of all, we focused our attention on lipid composition, namely cholesterol. We first realized that it affects the location of the protein in the membrane. Cholesterol, as it were, pushes out of the membrane and makes accessible to enzymes exactly those “wrong areas” that subsequently turn into plaques. We have shown which specific region of the protein interacts with cholesterol in the membrane and may be critical for plaque formation. If this is indeed the case (we still need to work to better prove this), then these regions of the amyloid-beta precursor protein could be considered as drug targets in the future. Relatively speaking, it will be possible to chemically influence them so that they “hide” again and do not become accessible prey for enzymes.

– Is it possible now, based on your preliminary findings, to say that high cholesterol can lead to Alzheimer’s disease?

– Not yet, – we did not consider the amount of cholesterol in the blood in our work. We simply looked at the interaction of this compound with the beta-amyloid precursor in the cell. But, given that the lipid composition of the cell still affects the formation of plaques, it can be assumed that in the future we will be able to choose a diet that will slow down the development of Alzheimer’s disease.