Microglia discovery offers clues to Alzheimer’s progression

Immune cells in the brain called microglia appear to control blood flow through capillaries, offering potential new treatment targets for Alzheimer’s and other brain disorders.

Researchers have shown that these immune cells, long known for their role in brain defence, also influence how capillaries supply oxygen and nutrients to brain tissue.

The discovery could inform therapies for Alzheimer’s disease, vascular dementia and Parkinson’s disease.

A team of researchers found that removing microglia caused capillaries to constrict and blood flow to fall.

Restoring the microglia reversed these effects, underlining their vital role in maintaining healthy brain circulation.

Dr Ukpong B. Eyo from the University of Virginia’s Neuroscience, said: “For some time now, microglia have been suggested to play important roles in regulating vessel function.

“With this study, we have provided the most definitive evidence that they do regulate blood flow to the brain, specified the location of this function to the brain’s small vessels or capillaries and identified an enzyme that they use to do this.”

Although the brain accounts for just 2 per cent of body weight, it consumes around 20 per cent of the body’s total energy.

This is delivered through a 400-mile-long network of blood vessels – with capillaries playing a critical role in distributing oxygen and nutrients.

Previous studies had linked dysfunction in myeloid cells – which include microglia – with reduced brain oxygenation and increased carbon dioxide levels.

Eyo’s team set out to pinpoint the exact cell type responsible and the effect of disrupting its function.

They discovered that microglia are essential in maintaining capillary “tone” – that is, the degree to which these tiny vessels are dilated or constricted

The study also identified a specific enzyme used by microglia to regulate this tone, which has been previously explored as a treatment target in Alzheimer’s – with mixed results.

First author Dr William A. Mills III said: “The microglial enzyme identified in this study has been targeted heretofore in patients with Alzheimer’s disease, albeit with mixed results.

“Our study suggests that these therapeutics would have maximal benefit if prescribed according to the therapeutic window of microglia in Alzheimer’s – a focus in our ongoing research.”

“We have determined that all microglia are capable of regulating basal capillary tone as opposed to a subset of them, thus revealing their importance to meeting energy demands in the brain,” Mills added.

The team now plans to study how microglia interact with other brain cells to support healthy blood flow – work that could lead to therapies to prevent or potentially reverse neurodegenerative disease.