Immune cells in the brain called microglia can partially break down large amyloid plaques characteristic of Alzheimer’s disease by latching on to them, forming a sort of external stomach and releasing digestive enzymes into the space, according to a preclinical study by Weill Cornell Medicine investigators. The findings could ultimately lead to therapies that boost the ability of microglia to break down amyloid plaques.
The study, published Dec. 6 in Cell Reports, shows that the breakdown process, called digestive exophagy, may also help explain seemingly contradictory reports that microglial cells can spread plaques in Alzheimer’s.
Microglia are scavengers that move around the brain, consuming small bits of cellular trash like microbes, dead cells and debris. They do this by wrapping themselves around the substance and encapsulating it in a vesicle. The vesicle then ferries the cargo to a membrane-bound organelle within the cell called a lysosome that is filled with digestive enzymes. Researchers suspected that microglia could also break down amyloid plaques, but it was unclear how the cells could consume these massive aggregates, which are much bigger than they are.
We found that the cells basically attach a lysosome onto a large plaque, and they expel enzymes into the space that can digest the amyloid.”
Dr. Frederick Maxfield, the Vladimir Horowitz and Wanda Toscanini Horowitz Distinguished Professor in Neuroscience at Weill Cornell Medicine
A familiar flavor
Thinking about how microglia could eat something very large in the brain reminded Dr. Maxfield of macrophages, which are immune