Two supporting cells, microglia and astrocytes, were found to communicate with each other.
Researchers from the Francis Crick Institute, the UK Dementia Research Institute at University College London and the VIB-KU Leuven Centre for Brain Disease Research have uncovered how communication between brain cells is linked to Alzheimer’s disease (AD).
Using a mouse model of AD, Cell Report It shows how communication between supporting cells in the brain can disrupt signals between nerve cells.
Currently the most common cause of dementia, AD is a progressive neurodegenerative disease that causes brain atrophy and brain cell death.
The scientists investigated the role of two supportive cells called astrocytes, which help neurons function, and microglia, immune cells in the brain that previous studies have shown to be involved in the development of AD.
Using a technique called spatial transcriptomics, the researchers mapped gene signals to different cell types and locations in the brain and found that while microglia accumulated near amyloid plaques throughout the mouse brain, astrocytes accumulated next to plaques in certain regions, such as the hippocampus.
Amyloid plaques, which play a central role in AD, are aggregates of misfolded proteins that form in the spaces between nerve cells.
The team then discovered that microglia and astrocytes communicate with each other: the more microglia there are around the plaques, the more toxic the astrocytes are to neurons, and the activated astrocytes disrupt nerve cell communication by increasing the chemical messenger GABA and decreasing another substance known as glutamate, resulting in reduced brain activity.
The researchers will now investigate the proteins involved and see whether they can block interactions between astrocytes and microglia.
“Both of these cells could be useful targets for treating Alzheimer’s disease,” said Lorena Carcamo, co-group leader of the AD Cellular Phase Lab at the Crick Institute. “We need to figure out how to specifically target the signals these cells produce near amyloid plaques in disease cases to understand whether we can reduce their detrimental effects on neurons.”
