Scientists discover new target for Alzheimer’s drugs

Stephen Back and Philip Adeniyi, OHSU School of Medicine

Researchers have discovered a new avenue of cell death in Alzheimer’s disease and vascular dementia.

A new study, led by scientists at Oregon Health & Science University (OHSU), has revealed that a form of cell death known as ferroptosis – caused by a build-up of iron in cells – destroys microglia cells, a type of cell involved in the brain’s immune response, in cases of Alzheimer’s and vascular dementia.

This finding will open new avenues in drug discovery for Alzheimer’s disease as potential new treatments could focus on reducing microglial degeneration in the brain.

The research uncovered a cascading form of neurodegeneration triggered by deterioration of myelin. They made the discovery using a novel immunofluorescence technique developed by the study’s lead author Philip Adeniyi, a postdoctoral researcher in Back’s laboratory.

The researchers discovered that microglia degenerates in the white matter of the brain of patients with Alzheimer’s and vascular dementia.

When myelin is damaged, microglia swarm in to clear the debris. In the new study, researchers found that microglia themselves are destroyed by the act of clearing iron-rich myelin (ferroptosis).

“This is a major finding,” said senior author Stephen Back, a neuroscientist and Professor of Pediatrics in the OHSU School of Medicine. “We’ve missed a major form of cell death in Alzheimer’s disease and vascular dementia. We hadn’t been giving much attention to microglia as vulnerable cells, and white matter injury in the brain has received relatively little attention.”

““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.”

Image shows: Stephen Back, a neuroscientist and Professor of pediatrics in the OHSU School of Medicine, left, and Philip Adeniyi, a postdoctoral researcher in Back’s laboratory. (Source: OHSU/Christine Torres HickP)

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