New study reveals how brain cell communication is linked to Alzheimer’s disease

Two support cells, microglia and astrocytes, were found to communicate with each other

Researchers at the Francis Crick Institute, University College London’s UK Dementia Research Institute and the VIB-KU Leuven Center for Brain and Disease Research have revealed how brain cell communication is linked to Alzheimer’s disease (AD).

Using mouse models with AD, the study published in Cell Reports shows how communication between support 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 the brain to shrink and brain cells to die.

Scientists investigated the role of two support cells known as astrocytes, which help neurons carry out their functions, and microglia, the immune cells in the brain, which have both been shown in previous research to be involved in the development of AD.

Using a technique called spatial transcriptomics, researchers mapped genetic signals to different cell types and their location in the brain and found that microglia built up near amyloid plaques all across the mouse brain, while astrocytes accumulated next to plaques in certain regions, such as the hippocampus.

Playing a central role in AD, amyloid plaques are aggregates of misfolded proteins that form in the spaces between nerve cells.

The team then found that the microglia and astrocytes were communicating with each other; the more microglia there was around the plaque, the more toxic to neurons astrocytes became, leading to reduced brain activity due to ‘activated’ astrocytes disrupting nerve cell communication by increasing GABA, a chemical messenger, and decreasing another known as glutamate.

Researchers now intend to investigate the proteins involved and see if they can block the cross-talk between astrocytes and microglia.

Lorena Cárcamo, co-group leader, Cellular Phase of AD Laboratory, the Crick, commented: “Both of these cells would be useful targets for Alzheimer’s treatments. We need to work out how to specifically target the signals they produce when found near amyloid plaques in the cases of disease and understand if we can reduce the harmful effects on neurons.”