Salk Institute Study Finds THC Reduces Alzheimer's-Related Proteins in Brain Cells

Salk Institute scientists have found preliminary evidence that tetrahydrocannabinol (THC) and other compounds found in marijuana can promote the cellular removal of amyloid beta, a toxic protein associated with Alzheimer's disease. The research, published in Aging and Mechanisms of Disease, represents a significant step toward understanding how cannabinoids might affect the disease process at a cellular level.

Understanding the Problem

Alzheimer's disease is a progressive brain disorder that affects more than five million Americans and is a leading cause of death. It is also the most common cause of dementia, with incidence expected to triple over the next 50 years. The disease is characterized by memory loss and severe impairment of daily functioning.

For years, scientists have known that amyloid beta proteins accumulate within nerve cells of the aging brain well before Alzheimer's symptoms appear. These proteins form the major component of plaque deposits that are a hallmark of the disease. However, the precise role of amyloid beta and the plaques it forms in the disease process has remained unclear.

The Salk Institute Discovery

In their laboratory study, the Salk team examined nerve cells that had been altered to produce high levels of amyloid beta to mimic aspects of Alzheimer's disease. They discovered that high levels of amyloid beta were associated with cellular inflammation and increased rates of neuron death.

The researchers then exposed these cells to THC and observed that it reduced amyloid beta protein levels and eliminated the inflammatory response caused by the protein. This allowed the nerve cells to survive, suggesting a potential protective mechanism.

"Although other studies have offered evidence that cannabinoids might be neuroprotective against the symptoms of Alzheimer's, we believe our study is the first to demonstrate that cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells," says Salk Professor David Schubert, the senior author of the paper.

The Role of Inflammation

One of the most significant findings of the study relates to inflammation within the brain. "Inflammation within the brain is a major component of the damage associated with Alzheimer's disease, but it has always been assumed that this response was coming from immune-like cells in the brain, not the nerve cells themselves," explains Antonio Currais, a postdoctoral researcher in Schubert's laboratory and first author of the paper.

When the researchers were able to identify the molecular basis of the inflammatory response to amyloid beta, they discovered that THC-like compounds that nerve cells make themselves may be involved in protecting the cells from dying.

The Endocannabinoid Connection

Brain cells contain receptors that can be activated by endocannabinoids, a class of lipid molecules made by the body for intercellular signaling in the brain. The psychoactive effects of marijuana are caused by THC, a molecule similar in activity to endocannabinoids that can activate the same receptors.

Physical activity results in the production of endocannabinoids, and some studies have shown that exercise may slow the progression of Alzheimer's disease. This connection suggests that the body's natural cannabinoid system may play a role in neuroprotection.

Related Research and Future Directions

The discovery about cannabinoids emerged from the team's study of J147, an Alzheimer's drug candidate developed at Salk that also removes amyloid beta from nerve cells and reduces inflammatory responses. The research on J147 led scientists to investigate how endocannabinoids are involved in removing amyloid beta and reducing inflammation.

Other authors on the paper include Oswald Quehenberger and Aaron Armando at the University of California, San Diego; and Pamela Maher and Daniel Daughtery at the Salk Institute. The study was supported by the National Institutes of Health, The Burns Foundation, and The Bundy Foundation.

Schubert emphasized that these findings were conducted in exploratory laboratory models, and that the use of THC-like compounds as a therapy would need to be tested in clinical trials before any conclusions about their effectiveness in humans could be drawn. The research provides a foundation for understanding the mechanisms by which cannabinoids might affect Alzheimer's disease at the cellular level, potentially opening new avenues for therapeutic development.