Biomedical researchers at Sanford Burnham Prebys have found that increasing levels of a natural brain protein called SORLA protects against toxic tau tangles, a primary driver of Alzheimer's disease and dementia.
The study, published in Science Advances on July 17, 2026, shows that elevated SORLA suppresses neurodegeneration by halting hyperphosphorylation and preventing abnormal tau proteins from spreading across neural networks.
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This reduces brain shrinkage and preserves vital synaptic connections.
While SORLA was previously known to prevent amyloid-beta accumulation, its protective role against tau-driven damage had remained largely unknown.
To analyze its effects, scientists crossbred genetically engineered mice possessing human SORLA with models displaying tau tangles and cognitive deficits.
"In the last 15 or 20 years, considerable data has come out from our lab and other groups showing that SORLA can suppress one of the hallmarks of Alzheimer's disease -- amyloid-beta generation and accumulation," said Timothy Huang, PhD, assistant professor in the Center for Neurologic Diseases at Sanford Burnham Prebys.
The research demonstrated that elevated protein levels effectively shielded communication junctions between neurons and reduced brain tissue loss.
"Very little was known, however, about whether SORLA affected the tau tangles reflected on the other side of the coin in Alzheimer's disease," said Tim Huang.
The findings indicated that boosting the protein led directly to measurable neuroprotective benefits in animal models.
"When you upregulate SORLA, you can suppress the negative effects found in tauopathies," said Huijie Huang, PhD, a staff scientist in the Huang lab at Sanford Burnham Prebys and lead author of the study.
