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Göttingen – The protein beta-amyloid plays a key role in Alzheimer’s disease. It accumulates in those affected to form insoluble clumps, settles in the form of plaques between nerve cells in the brain and damages them. A working group at the Max Planck Institute (MPI) for Multidisciplinary Sciences has now shown that not only nerve cells but also glial cells in the brain produce beta-amyloid proteins. This could offer approaches for future therapies, the researchers report in the specialist journal Nature Neuroscience (2024, DOI: 10.1038/s41593-024-01730-3).

The cells of the nervous system produce beta-amyloid by splitting a larger precursor molecule. One of the most important helpers is the enzyme BACE1. For their experiments, the research team specifically switched off BACE1 in nerve cells and oligodendrocytes of mice. They then examined plaque formation in the entire brain using a special microscopy technique.

It was shown that nerve cells are the main producers of beta-amyloid. “But oligodendrocytes also produce a considerable amount of the protein that is incorporated into plaques,” said Andrew Octavian Sasmita. He is the first author of the study together with Constanze Depp.

“When BACE1 was missing in oligodendrocytes, about 30 percent fewer plaques were formed. In nerve cells in which the BACE1 gene was switched off, this reduced plaque formation by over 95 percent,” explained Depp. The researchers also found that plaque deposits only form when a certain amount of beta-amyloid is present. The oligodendrocytes apparently contribute to this.

This threshold could be helpful for Alzheimer’s therapies. If BACE1 could be inhibited before this threshold is reached, the plaques might not form until later, said Klaus-Armin Nave, director at the MPI for Multidisciplinary Sciences. The researchers hope that this could help slow the progression of Alzheimer’s disease in the early stages. © hil/aerzteblatt.de