Researchers studying the effects of immune cells surrounding blood vessels in the brain have discovered a new pathway involving these cells that may contribute to the cause of Alzheimer’s disease.
One of the hallmarks of Alzheimer’s disease is the accumulation of plaque deposits, or abnormal protein fragments, from a peptide called amyloid-beta. Amyloid-beta destroys neurons and damages brain blood vessels with the help of highly reactive molecules, called free radicals, which are derived from oxygen. In the study published in Circulation Research, the researchers sought to determine which cells in the brain were responsible for producing the free radicals, also known as reactive oxygen species (ROS).
The free radicals paralyze the vessels, preventing normal function. As a result, the brain cells are deprived of the oxygen and glucose they need to function correctly.
The investigators examined cells in the brain called perivascular macrophages (PVM), which surround blood vessels and pick up and remove damaging metabolic byproducts floating around the brain. The team focused on these cells because amyloid-beta tends to accumulate in the vascular space where PVM are located. They noticed that when cells are exposed to amyloid beta, the PMV begin to produce large quantities of free radicals.
To determine whether the PVM were involved in the ROS production, the researchers removed PVM by injecting into the brains of mice spherical lipid droplets called liposomes that contained the drug clodronate.
Researchers administered the liposomes in mice with Alzheimer’s disease; ROS paralyzed the blood vessels in the rodents. Remarkably, the team found that the blood vessels in these mice appeared to work normally once rid of PVM, despite the presence of amyloid-beta, demonstrating that without the PVM, amyloid beta did not exert its damaging effect on brain blood vessels.
Genetic studies have long suggested that the brain’s innate immune cells, like microglia and macrophages, contribute to Alzheimer’s disease, but how these cells damaged the brain was not known. The study demonstrates a novel way in which immune cells could contribute to Alzheimer’s disease and offer a new approach to treatment.
Reprinted from materials provided by Cornell University.