In collaboration with researchers at Edinburgh University, work funded partly by MND Scotland, they have discovered that a specific type of brain cell called ‘microglia’ can become overactive in neurodegenerative disease and destroy the small points of contact between brain cells, called synapses.
We already know that Amyotrophic Lateral Sclerosis (ALS), the most common form of Motor Neurone Disease, is characterized by extensive synaptic loss but we don’t know what causes this. The new study used a mouse model in which a known ALS gene called TDP-43 was switched off only in microglia. These mice had overactive microglia which chewed up synapses. When these mice were bred with an Alzheimer’s Disease mouse, the microglial cells increase the clearance of the abnormal clumps of proteins which are found in Alzheimer’s Disease. However, they also caused a significant loss of synapses. While mopping up toxic protein clumps in neurons is highly desirable, the loss of synapses is certainly not.
Next, the researchers checked if something similar happened in the brains of ALS patients. They found that ALS patients with high levels of TDP-43 pathology, had more overactive microglia in their brain. Interestingly, ALS patients tended to have a lower amount of Alzheimer’s-related protein clumps in the brain, possibly due to the actions of these overactive microglia.
These exciting results suggest that microglial cells are emerging as key players in neurodegenerative disorders such as ALS.
Chris Henstridge | University of Edinburgh