Israeli Scientists Discover Mechanism That Could Slow Pace of Alzheimer's

Weizmann Institute researchers identify a new type of cells that attacks plaque build-up in brains of those with the neurodegenerative disease

An MRI, or magnetic resonance imaging, machine in Jerusalem's Shaare Zedek Medical Center, which is often used in brain research.

A previously unknown type of immune cells has been discovered in the brains of Alzheimer’s patients by Israeli scientists at the Weizmann Institute in Rehovot. The development of these cells, called microglia, is triggered by the disease itself. The researchers now believe that they can be effective in ridding the brain of the plaque that clogs it up in those suffering from Alzheimer's.

The hope is that if these cells can be kicked into higher gear somehow, it could help the body stave off the damage caused by the neurodegenerative disease, which remains incurable.

Alzheimer's is characterized by pathological processes that gradually impair the functioning of the brain over time by means of multiple mechanisms. One is nerve-cell death, which occurs as the cytoskeletal proteins lose their normal structure. Another is the buildup of goo inside and between the cells; the goo is a beta-amyloid protein that hardens into plaques. Neural signaling is also impaired: Alzheimer’s disrupts the movement of electrical charges between nervous cells through the gaps between them, the synapses, and also disrupts neurotransmitter chemicals.

What the Weizmann scientists did is identify microglia that are not found in healthy brains, which gradually change with the advance of the disease. Hence, they called them DAM, disease-associated microglia – the brain’s mechanism for trying to get rid of that plaque.

To be clear, the research has been conducted to date on mice, not human beings. The healthy non-Alzheimer's animals were found not to have the DAM cells in their brains.

When do our brains, or mouse brains, start producing DAM? When there is diminished expression of the proteins that usually restrain ordinary immune-system activity in the brain, explain the scientists. It also requires an increase in the expression of a proteins, including one called TREM2 – a mutation that is accompanied by an early, and dramatic, onset of Alzheimer’s.

In mice that were engineered not to have any TREM2 protein, microglia did not metamorphose into DAM cells that could help remove the Alzheimer's plaque.

Further study showed that TREM2 could only be found, in mice and men, in proximity to the plaque.

“It was like a detective story,” says Prof. Ido Amit, who participated in the Weizmann study along with colleague Michal Schwartz.

The upshot is that the brain does seem to know how to handle plaque that accumulates as a result of Alzheimer's, but sometimes it can’t keep up with the pace of the disease. Prof. Schwartz notes, however, that the team's discoveries, and the new information about the role played by the microglia, could eventually lead to new treatment for the disease.