Study reveals brain’s defense against Alzheimer’s

Researchers at the Sanford Burnham Prebys Medical Discovery Institute in California have found that increasing levels of a naturally occurring protein known as SORLA may significantly reduce the toxic protein tangles associated with Alzheimer’s disease, potentially opening new avenues for the development of more effective treatments for the currently incurable neurodegenerative disorder.

SORLA is a complex protein found primarily in the central nervous system. It is produced naturally by the body and cannot be obtained from external sources such as dietary supplements or food.

In Alzheimer’s disease, the tau protein loses its normal role in maintaining the structure and stability of brain cells. Instead, it becomes abnormally twisted and forms structures known as tau tangles. These toxic aggregates damage neural connections, trigger cell death and contribute to progressive cognitive decline and memory loss.

Alzheimer’s disease is characterized by a gradual deterioration of neurological function over time, eventually leading to brain shrinkage and the loss of cognitive abilities. It is the most common cause of dementia, an umbrella term describing a range of symptoms caused by physical damage to the brain, and accounts for an estimated 60% to 70% of dementia cases worldwide.

Although SORLA was previously known for its ability to limit the accumulation of amyloid-beta, another major hallmark of Alzheimer’s disease alongside tau tangles, its effects on tau pathology had remained unclear.

In the study, published in the journal Science Advances, researchers engineered genetically modified mice to produce elevated levels of human SORLA alongside tau tangles, creating a model designed to mimic key features of Alzheimer’s disease in humans.

The findings showed that higher SORLA levels actively protected the brain against several biological drivers of neurodegeneration. Elevated SORLA reduced hyperphosphorylation, a chemical process that promotes the aggregation and tangling of tau protein, and prevented abnormal tau from spreading through neural networks.

The mice with increased SORLA levels also showed significantly less brain atrophy, reduced tau accumulation and substantially better preservation of synapses—the vital points of contact that enable brain cells to communicate with one another.

By contrast, when researchers examined mice completely lacking the gene responsible for producing SORLA, neurodegeneration and cellular damage worsened significantly, further confirming the protein’s key protective role.

“When you increase SORLA levels, you can suppress the harmful effects associated with tau protein diseases,” said Dr. Huijie Huang, a researcher at Sanford Burnham Prebys and the study’s lead author. “We observed less brain atrophy and less tau accumulation, and that was extremely exciting.”

Dr. Timothy Huang, an associate professor at the institute and co-author of the study, said the findings could potentially pave the way for the use of existing drugs to reverse some symptoms of the disease, representing a potential shift in treatment strategies.

Further research will be needed to determine whether these findings can be translated into safe and effective treatments for humans. However, the study provides a promising roadmap for therapies designed to protect memory and halt the neurodegenerative effects of Alzheimer’s disease, for which there is currently no known cure.