Before we can develop a cure for Alzheimer's and related dementia diseases, we need to figure out how they get started and how they develop in the brain. A newly discovered chemical pathway could offer up some clues.
Scientists from the Oregon Health and Science University (OHSU), the University of Washington, and the Allen Institute for Brain Science have uncovered a previously undescribed way immune cells can be destroyed in the brains of people with Alzheimer's and vascular dementia (dementia related to a lack of blood flow to the brain).
"We've missed a major form of cell death in Alzheimer's disease and vascular dementia," says neuroscientist Stephen Back, from OHSU. "We hadn't been giving much attention to microglia as vulnerable cells, and white matter injury in the brain has received relatively little attention."
Through the study of brain tissue of people with dementia after their death, the researchers found a chain reaction of events causing damage to the bridges of 'white matter' that link different parts of the brain.
It starts with myelin, which forms protective sheaths to keep neurons protected and help them communicate more efficiently. When myelin layers become worn out – in part due to aging, factors like hypertension – they are cleared from the brain by immune cells called microglia.
The researchers discovered that the microglia cells themselves are also destroyed as they sweep away the damaged myelin, seemingly by overdosing on iron that is contained within the white matter in significant quantities. In effect, the scientists say, the microglia immune cells are dying in the line of duty as they try to keep the brain safe.
"Everyone knows that microglia are activated to mediate inflammation," says Back. "But no one knew that they were dying in such large numbers. It's just amazing that we missed this until now."
The cascading effect of microglia death and white matter degeneration appears to play a part in the cognitive decline linked to Alzheimer's and vascular dementia, according to the new study – though further research will be required to know for sure.
Now we know more about this microglial degeneration, we might be able to develop drugs and treatments to do something about it – perhaps helping to slow or block the cognitive decline associated with Alzheimer's and related diseases.
"That's where the field will go next," says Back. "A discovery like ours will stimulate a lot of excitement in the pharmaceutical industry to develop therapeutically important compounds."
The research has been published in Annals of Neurology.