Over 55 million people worldwide have dementia. AD is the most common form of the disease and, according to the World Health Organization, may constitute 60-70% of cases. Amyloid beta protein plays a central role in AD, accumulating in insoluble plaques between the brain's neurons.
In previous research, the scientists behind the current study found that defective myelin from glial cells called oligodendrocytes exacerbate Alzheimer's disease. Oligodendrocytes form myelin, an insulating fatty layer that wraps around nerve fibers to facilitate signal transmission. In the current study, the researchers investigated the role of glial cells in amyloid beta production in AD.
Cells in the nervous system generate amyloid beta by cleaving a larger precursor molecule with the aid of an enzyme known as BACE1. In experiments, the researchers knocked out BACE1 in the neurons and oligodendrocytes of mice. They then studied plaque formation in the brain via 3D light-sheet microscopy.
"Oligodendrocytes lacking BACE1 developed about 30 percent fewer plaques. Knocking out the BACE1 gene in neurons reduced plaque formation by over 95 percent," said first author of the study, Constanze Depp, a former PhD student at the Max Planck Institute (MPI) for Multidisciplinary Sciemces in Gottingen, Germany, in a press release.
The findings show that neurons are the main producers of amyloid beta, However, they also demonstrate that oligodendrocytes produce significant quantities of the protein that are incorporated into plaques. The researchers noted that plaque deposits only form in the presence of a certain amount of neuronal amyloid beta, and that oligodendrocytes contribute to these plaques.
Awareness of this threshold could be useful for the development of AD therapies. Study author Klaus-Armin Nave, Director at the MPI for Multidisciplinary Sciences, said in a press release that inhibiting BACE1 before this threshold is reached could delay the formation of plaques. This could then help slow the progression of AD at an early stage.
Sources: Neuroscience News, Nature Neuroscience
