In Alzheimer’s disease, special protein deposits (tau and beta-amyloid plaques) in the brain are considered to play an important role. Immunotherapy to activate microglia using an antibody could reduce such beta-amyloid plaques in the brain.
A research team at Washington University School of Medicine in St. Louis has demonstrated in mice that treatment with an anti-human LILRB4 monoclonal antibody (mAb) reduces beta-amyloid burden and behavioral abnormalities in Alzheimer’s disease. The corresponding study results are published in the specialist journal “Science Translational Medicine”.
Alzheimer’s and beta amyloid
Alzheimer’s disease begins with a sticky protein called beta-amyloid, which builds up into plaques in the brain and triggers a chain of events that leads to brain atrophy and cognitive decline, the researchers explain.
Current therapeutic approaches have focused on reducing these protein deposits, although a recently published study, for example, has also shown that ultrasound therapy has a promising effect against Alzheimer’s without reducing beta-amyloid deposits.
New immunotherapy
Now researchers at Washington University School of Medicine in St. Louis have found a new, promising way to remove the harmful plaques in the brain by directly mobilizing immune cells to consume them.
Microglia are special immune cells of the central nervous system. They surround the plaques and form a barrier that controls the spread of the harmful protein, explains the research team.
Normally they can also engulf and destroy the plaque proteins, but in Alzheimer’s disease this process is impaired. The team explains that the cause of this could be a protein called APOE, which is part of amyloid plaques.
Immune cells inactivated
The APOE proteins in the plaque bind to a receptor – LILRB4 – on the microglia surrounding the plaque and inactivate them, the researchers continue. This inhibits their ability to control harmful plaque formation.
Treating mice that had amyloid-beta plaques in their brains with a special antibody that blocked APOE from binding to LILRB4 resulted in activated microglia being able to engulf and destroy the amyloid-beta plaques eliminate, the team reports.
The elimination of the amyloid beta plaques also reduced the behavioral changes typical of Alzheimer’s in the mice.
If this therapeutic benefit is confirmed in further human studies, the approach could open up completely new perspectives not only in the treatment of Alzheimer’s, but also in other neurodegenerative diseases that are associated with protein deposits.
“By generally activating microglia, our antibody can remove amyloid beta plaques in mice and potentially eliminate other harmful proteins in other neurodegenerative diseases, including Parkinson’s disease,” explains study author Professor Marco Colonna. (fp)
