Israeli scientists have described the mechanism of spread of toxic proteins that cause Alzheimer’s disease

A research team led by Professor Michael Glickman, Dean of the Technion’s Faculty of Biology, has identified a key mechanism in the development of Alzheimer’s disease. The cellular system, designed to utilize toxic proteins, in certain situations simply throws them outside the cell. This discovery explains how a disease that starts randomly in a few neurons can spread to large areas of the brain.

In a paper published in the journal PNAS, Professor Glickman and colleagues describe how brain cells cope with UBB+1, a defective and toxic variant of the ubiquitin protein. The ubiquitin system is essential for breaking down damaged proteins, but when ubiquitin mutates to UBB+1, it begins to damage the cell by forming protein aggregates associated with the development of Alzheimer’s. For neurons that do not divide or regenerate, this is deadly.

The p62 protein, involved in the process of “cell suicide,” acts as a receptor that recognizes UBB+1 and encloses it in a vesicle. The next step is that p62 either directs this vesicle to the cellular processing center or throws it out into the interstitial fluid of the brain. Researchers have shown that the second option can threaten brain tissue: fragments of the toxic UBB+1 protein penetrate into neighboring neurons, accelerating the spread of Alzheimer’s pathology.

“We all take out trash, but in this case, cells dump their trash directly on the heads of their neighbors,” explains Professor Glickman. “While this solves the problem for an individual cell, it can cause long-term damage to the entire tissue. We believe that uncovering this mechanism will allow, firstly, early diagnosis of Alzheimer’s disease based on cerebrospinal fluid tests, and secondly, the development of precise, personalized treatments.”