Before we can devise a remedy for Alzheimer’s and related dementia disorders, we must unravel their origins and progression in the brain. A recently identified chemical pathway could provide valuable insights. Scientists from the Oregon Health and Science University (OHSU), the University of Washington, and the Allen Institute for Brain Science have unveiled a previously unknown method by which immune cells can perish in the brains of individuals with Alzheimer’s and vascular dementia (a form of dementia linked to reduced blood flow in the brain).
Neuroscientist Stephen Back from OHSU remarks, “We’ve overlooked a significant type of cell death in Alzheimer’s disease and vascular dementia. We hadn’t been paying much attention to microglia as vulnerable cells, and brain white matter injury has received relatively little attention.”
Microglia are activated to mediate inflammation
By analyzing brain tissue from deceased individuals with dementia, the researchers identified a sequence of events that leads to damage in the ‘white matter,’ which connects different brain regions.
The process begins with myelin, which forms protective sheaths around neurons to safeguard them and facilitate more efficient communication. When these myelin layers deteriorate – partly due to aging and factors like hypertension – they are eliminated from the brain by immune cells called microglia.
The researchers found that the microglia cells themselves are destroyed while removing damaged myelin, seemingly due to an excess of iron present in significant quantities within the white matter. In essence, the scientists suggest that microglia immune cells are sacrificing themselves while trying to safeguard the brain. Back explains, “Everyone knows that microglia are activated to mediate inflammation. But no one knew that they were dying in such large numbers. It’s just amazing that we missed this until now.”
Stimulate a lot of excitement in the pharmaceutical industry
According to the new study, the cascading impact of microglia death and white matter degeneration appears to contribute to the cognitive decline associated with Alzheimer’s and vascular dementia – although further research is necessary for confirmation.
With a better understanding of this microglial degeneration, we may be able to develop drugs and treatments to address it, potentially slowing or halting the cognitive decline associated with Alzheimer’s and related conditions. Back anticipates, “That’s where the field will go next. A discovery like ours will stimulate a lot of excitement in the pharmaceutical industry to develop therapeutically important compounds.”