Brain’s Support Cells May Be Behind Disease: ScienceAlert

Neurons aren’t the only brain cells that produce proteins associated with Alzheimer’s disease, a new study in mouse models reveals. It turns out that the cells that support neurons also contribute to the process.

Beta-amyloid proteins occur naturally in our brains, but have long been controversially associated with Alzheimer’s disease.

“Until now, it was thought that neurons were the main producers of beta-amyloid and that they were the main target for new drugs,” says molecular biologist Klaus-Armin Nave of the Max Planck Institute for Multidisciplinary Sciences in Germany.

Treatments targeting these proteins have not been as successful as hoped, indicating that we are still missing crucial components of this disease.

The fact that there are other factors contributing to beta-amyloid clumps may provide much-needed clues.

With a new dementia diagnosis now made every three seconds, more and more of us are experiencing frightening symptoms of confusion, communication difficulties and memory loss, either personally or in those we love.

Andrew Octavian Sasmita, a neurogeneticist at Max Planck University, and his colleagues have demonstrated the involvement of neuron support cells, oligodendrocytes, in the abnormal formation of brain plaques by suppressing their ability to create beta-amyloid.

They achieved this by knocking out the gene responsible for the APP beta-cleaving enzyme (BACE1). As its name suggests, BACE cleaves the beta-amyloid precursor protein (APP), which is involved in the production of beta-amyloid protein.

“Oligodendrocytes lacking BACE1 developed about 30 percent fewer plaques,” says Constanze Depp, a neurogeneticist at Max Planck.

Although BACE1 inhibition typically results in a much greater reduction in plaque formation (over 95%) in mice, BACE inhibition appears to cause other debilitating problems, including worsening memory and decreased brain volume in human clinical trials.

This is likely because BACE1 is involved in neuron proliferation in adult mice. But when Sasmita and his team knocked out BACE1 only in oligodendrocyte cells, they saw no disruption in neuron number or distribution.

“Potentially, selective targeting of BACE1 in oligodendrocytes could avoid the drawbacks of generalized BACE1 inhibition,” the researchers write in their paper.

Other researchers are now warning that continued focus on amyloid beta proteins could keep us on the wrong track, as these plaques may be just a side effect rather than the cause of Alzheimer’s disease.

However, previous research has also implicated oligodendrocytes in Alzheimer’s disease.

“One of the jobs of oligodendrocytes is to form myelin – an insulating layer – and wrap it around nerve fibres to speed up signal transmission,” Sasmita explains.

This process also appears to be disrupted in mouse models of Alzheimer’s disease, suggesting that even if amyloid beta eventually proves to be a dead end, oligodendrocyte cells may still play a role in causing this stubbornly incomprehensible disease.

This research was published in Neuroscience of Nature.