Neurodegenerative diseases are currently the most common cause of dementia.
Research led by the UK Dementia Research Institute (UK DRI) and University College London (UCL) suggests that targeting amyloid beta production in one type of cell in the brain could potentially improve the early stages of Alzheimer’s disease (AD) with fewer side effects.
Published in a journal PLOS BiologyThe findings suggest that specifically targeting amyloid-β production from oligodendrocytes may be a promising therapeutic strategy for treating neurodegenerative diseases.
Currently the most common cause of dementia, AD is a progressive neurodegenerative disease that causes brain atrophy and brain cell death.
The accumulation of misfolded amyloid-β is recognized as one of the hallmarks of Alzheimer’s disease, which is thought to be driven by neurons.
The researchers aim to test whether oligodendrocytes, the nerve cells that produce myelin, the insulating material that surrounds the processes (axons) that transmit impulses between neurons, produce harmful amyloid-beta and whether it plays a role in neuronal dysfunction in early Alzheimer’s disease.
Using postmortem brain tissue from people with and without Alzheimer’s disease, the researchers looked at the expression levels of genes involved in the production of amyloid-beta in different cell types.
The researchers found that oligodendrocytes contain the genes necessary to make this harmful protein, and found that tissue from Alzheimer’s patients had increased numbers of oligodendrocytes expressing genes linked to amyloid-β production. Notably, human oligodendrocytes produced more amyloid-β per cell than neurons.
Using a mouse model of Alzheimer’s disease, the researchers found that amyloid beta produced by oligodendrocytes is associated with the formation of plaques. The team found that by inhibiting the production of amyloid beta protein in oligodendrocytes, they were able to restore normal neuronal activity in the mouse brain.
Marc-Aurel Bouchet, UCL, UK DRI group leader, said: “We have shown that oligodendrocytes produce amyloid-beta and that simply inhibiting this process rescues early functional impairment in mice. This suggests that by targeting amyloid-beta production in just one type of cell in the brain, we may be able to improve early disease outcomes.”
