Are prions involved in Alzheimer's disease?

Alzheimer's proteins spread like prions in the brain

For the first time, researchers have observed directly how Alzheimer's disease spreads from brain cell to brain cell. According to this, thread-like, malformed protein molecules transmit dementia within the brain. They jump over wherever two cells touch each other, as the Swedish scientists discovered in cell culture experiments. Once the brain cells had absorbed the disease-causing protein, they perished. So far it was not known how Alzheimer's got from one brain region to the next. The results now show that the malformed protein threads are the transmitter and that direct connections between the brain cells are the transmission path, the researchers report in the journal "Journal of Neurology". The spread of Alzheimer's is in many ways similar to that of misfolded prions in the brain of cattle with BSE.

According to the researchers, the new findings represent an important advance in Alzheimer's research. If you now analyze the transmission mechanism even more closely, it opens up new ways to prevent the spread of Alzheimer's in the brain. “This makes it easier to develop therapies that can stop the progression of this disease,” write Martin Hallbeck and his colleagues from Linköping University in Sweden.

It has long been known that Alzheimer's disease gradually spreads from one brain region to the next. Large, clumped protein deposits, the so-called beta-amyloid plaques, form in the affected areas and the brain cells die. How the disease is transmitted in the brain was not yet known, say Hallbeck and his colleagues. However, there were indications that a preform of the plaques was involved. This preform consists of thread-like, malformed beta amyloid proteins. In their experiment, the researchers have now demonstrated how these thread molecules act as carriers for Alzheimer's in the brain.

Red marking indicates passing on of the protein threads

For their study, the researchers used cell cultures with both mouse brain cells and those with human brain cells. First, they marked malformed protein threads with a red dye. They injected these proteins directly into some of the brain cells of the two cell cultures with an extremely fine needle. The next day, the neighboring brain cells connected by runners were also colored red, report Hallbeck and his colleagues.

After a further two days, the infected cells showed clear signs that they were beginning to decay. Its long runners gradually lost their shape. Inside the cells, individual vesicles and cell parts began to dissolve and leak. "Little by little, more and more cells became sick," reports Hallbeck. Those brain cells that were not in contact with the infected cells, on the other hand, had not absorbed any protein threads and did not become ill either. This shows that the transfer is based on direct connections between the cell extensions, say the researchers.

How exactly this transfer takes place is still unclear. However, the cell culture experiments already provided initial indications that infected brain cells collect and release the disease-causing proteins in small membrane vesicles. These are then apparently transported to the neighboring cells and taken up by them. How this works and where this transfer can be blocked must now be examined more closely, the researchers believe. (doi: 10.1523 / JNEUROSCI.0615-12.2012)

(Journal of Neurology, June 27, 2012 - NPO)

June 27, 2012