A brain protein slows tau damage in Alzheimer mice

In Alzheimer’s and related brain conditions, tau proteins become chemically altered. They then aggregate into structures called neurofibrillary tangles. These tangles damage neurons and disrupt their normal function. As the disease progresses, more and more brain cells die.

The researchers found that a protein called SORLA (encoded by the SORL1 gene) plays a role in the transport and clearance of tau inside neurons. SORLA is part of a cellular sorting system that determines where proteins go within the cell. In Alzheimer’s patients, SORLA production is reduced. This was already known in relation to amyloid-beta, another protein aggregation involved in Alzheimer’s, but the link with tau had been less well studied.

What does the animal model show?

In mice genetically engineered to develop tau pathology (the PS19 model), increased SORLA expression slowed tau accumulation and synapse loss, where synapses are the connections between neurons. It also reduced overactivation of glial cells, the brain’s support cells that can themselves contribute to damage when chronically activated. Memory in the animals appeared better protected in early measurements. The study was published in Science Advances.

These are findings from a mouse model, not from humans. The step toward an effective treatment in people is large and uncertain. That SORLA has already been genetically linked to Alzheimer’s risk through large-scale genetic studies (GWAS) does give the finding additional scientific weight.

A new route to treatment?

If SORLA expression can be increased via a drug or gene therapy, it might be possible to slow tau pathology. That remains a hypothetical scenario, but it offers a concrete biological target. Research into SORL1 as a therapeutic target now stands on somewhat firmer ground.

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