A natural protein found in the brain could offer a powerful new defence against the damage caused by Alzheimer’s disease, according to a new breakthrough study.
Researchers at Sanford Burnham Prebys, a biomedical research facility in California, have discovered that boosting levels of a protein known as SORLA (sorting-related receptor with A-type repeats) can significantly suppress the toxic protein tangles linked to neurodegeneration.
SORLA is a complex, essential protein primarily found in the central nervous system. It is produced by the body, and cannot be consumed through external sources.
In Alzheimer’s disease, a protein known as tau breaks away from its normal role of stabilising brain architecture. Instead, it twists into abnormal knots called tau tangles. These toxic clumps then destroy neural connections, trigger cell death, and drive cognitive decline.
Alzheimer’s disease currently affects roughly 800,000 people in the UK, according to the NHS. The condition sees a progressive reduction in neural function over time, resulting in brain shrinkage.
It the most common cause of dementia, the wider umbrella term used to describe a collection of symptoms caused by physical damage to the brain, and accounts for roughly 60 to 70 per cent of all cases worldwide.
While SORLA was already known to limit the accumulation of amyloid-beta — the other primary hallmark of Alzheimer’s — its impact on tau tangles remained unclear until now.
In the study, published in Science Advances, researchers genetically engineered mice to produce higher levels of human SORLA alongside tau tangles.
The results showed that elevating SORLA actively guarded the brain against several biological drivers of neurodegeneration.
Higher SORLA levels reduced hyperphosphorylation — a chemical process that causes tau to clump together — and prevented abnormal tau from spreading throughout neural networks.
Mice with boosted SORLA experienced significantly less brain shrinkage, lower tau buildup, and far better preservation of their synapses, the vital junction points that allow brain cells to communicate.
Conversely, when researchers examined mice completely lacking the gene for SORLA, neurodegeneration and cellular damage worsened significantly.
"When you upregulate SORLA, you can suppress the negative effects found in tauopathies," said Dr Huijie Huang, staff scientist at Sanford Burnham Prebys and lead author of the study.
"We found there was less brain atrophy and less tau accumulation, which was very exciting to see," Dr Huang added.
These findings could potentially open the door to using existing drugs to reverse disease symptoms, pointed out Dr Timothy Huang, assistant professor at Sanford Burnham Prebys and co-author of the paper.
The current treatment landscape for Alzheimer’s has been focused on slowing cognitive and functional decline, with interventions like Leqembi and Kisunla enjoying various levels of success.
However, fewer studies have focused on reversing the damage, marking this study as a significant advance in neurological research.
While further research is needed to translate these findings into human therapies, the study has created a promising roadmap for therapies designed to protect memory and halt the neurodegenerative effects of Alzheimer’s.
With no known cure, dementia remains the leading cause of death in the country, according to figures provided by Alzheimer’s research UK.
