Study suggests targeting amyloid beta production could be promising in AD

The neurodegenerative disease is currently the most common cause of dementia

A study led by the UK Dementia Research Institute (UK DRI) and University College London (UCL) has suggested targeting amyloid beta production in one cell type in the brain could improve early disease outcomes, with fewer side effects, in Alzheimer’s disease (AD).

Published in the journal PLOS Biology, findings suggest that targeting the production of amyloid beta specifically from oligodendrocytes could be a promising therapeutic strategy for treating the neurodegenerative condition.

Currently the most common cause of dementia, AD is a progressive, neurodegenerative disease that causes the brain to shrink and brain cells to die.

Accumulation of misfolded amyloid beta is recognised as one of the hallmarks of AD, which is believed to be caused by neurons.

Researchers aim to test whether oligodendrocytes, a neural cell that produces myelin, the insulating material that surrounds the projections that transfer impulses between neurons, called axons, could produce harmful amyloid beta and whether they play a role in neuronal dysfunction in early AD.

Using post-mortem brain tissue from people both with and without Alzheimer’s pathology, researchers examined the expression levels of genes involved in the production of amyloid beta across different cell types.

They discovered that oligodendrocytes contained the genes needed to produce this harmful protein and in the tissue of people who had AD, researchers found an increase in the number of oligodendrocytes expressing genes related to amyloid beta production – human oligodendrocytes in particular produced more amyloid beta per cell than neurons.

After using mouse models of AD, researchers discovered that amyloid beta produced by oligodendrocytes was associated with the formation of plaques. The team found that by blocking the production of the amyloid beta protein in oligodendrocytes, they could restore normal neuronal activity in the brains of mice.

UK DRI group leader Marc Aurel Busche, from UCL, commented: “We have shown that oligodendrocytes produce amyloid beta and that suppressing this process is enough to rescue early dysfunction in mice…, suggesting that targeting amyloid beta production in just one cell type in the brain might improve early disease outcomes.”