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How do specialized brain cells contribute to problems with nerve cell communication in Alzheimer’s?
Soyon Hong, Ph.D.
University College London, UK DRI at UCL
London, United Kingdom
Background
Microglia are the primary immune cells of the brain. They play a major role in helping to maintain healthy nerve cells, in part by removing unwanted material from the brain. During Alzheimer’s, microglia can become overactivated. Research by Dr. Soyon Hong and others has shown microglia affected in Alzheimer’s sometimes remove the specialized structures nerve cells use to send signals to one another and communicate, known as synapses.
It is not entirely clear what triggers microglia to remove synapses. However, initial work by Dr. Hong has shown that certain helper cells in the brain, known as astrocytes, may be involved. Astrocytes in older and diseased brain tissue have elevated levels of proteins associated with similar removal processes. One protein that is particularly elevated is known as milk fat globule-EGF factor 8 (MFG-E8).
Research Plan
Dr. Hong will test whether MFG-E8 from astrocytes assists with the microglia’s ability to remove synapses in mouse models of Alzheimer’s. The research team will use specialized genetic techniques to lower levels of MFG-E8 in the brains of mice with Alzheimer’s-like disease. The researchers will then compare synapse loss in the mice with lower levels of MFG-E8 to mice with normal amounts of MFG-E8. They will use specialized microscope techniques to look inside astrocytes collected from the mice for parts of engulfed synapses. Dr. Hong also plans to test whether astrocytes from the brains of individuals who had Alzheimer’s produce MFG-E8.
In the second part of the study, Dr. Hong’s team will use a microscope technique that can record live cells inside brain tissue. The researchers will expose brain tissue to beta-amyloid, a hallmark protein of Alzheimer’s, and then monitor any astrocyte-microglia interactions, particularly near synapses. As a final step, Dr. Hong’s team will measure gene (RNA) levels in astrocytes including the gene encoding MFG-E8.
Impact
This study could uncover ways synapses become impaired by immune cells in the brain during Alzheimer’s. It may also identify molecular pathways that might serve as therapeutic targets to delay or prevent nerve cell damage in Alzheimer’s.
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