An experimental drug has demonstrated the ability to reduce amyloid beta levels by approximately 50 percent in aged rats, according to new research from the Keck School of Medicine of USC. The study, published in the Journal of Biological Chemistry, suggests that targeting the liver rather than the brain could provide a new pathway for preventing Alzheimer’s disease and heart disease.
The research focused on the liver’s role in clearing harmful substances from the body. Researchers found that the experimental drug cinaciguat reverses certain effects of aging in the liver, which may lower the risk of clogged arteries and Alzheimer’s. This approach addresses a significant hurdle in neurology: treatments targeting the brain currently face a 98% failure rate in clinical trials, largely because it is obnoxiously difficult to deliver drugs across the blood-brain barrier.
Restoring Liver Filter Cells
The study specifically examined liver sinusoidal endothelial cells (LSECs), a specialized population of cells that line the liver’s blood vessels. These cells function like tiny sieves, containing microscopic holes that allow molecules to pass from the blood into liver cells for processing. As organisms age, these holes tend to narrow or disappear, weakening the liver’s ability to purify the blood.
By administering cinaciguat to aged rats for two weeks, researchers observed an improvement in the structure and function of these endothelial cells. The treatment helped restore the microscopic holes, which coincided with a 50% reduction in amyloid beta levels in the blood, bringing them closer to levels seen in younger animals.
Unexpected Impact on Cholesterol
In a surprising finding, the researchers noted that cinaciguat also reduced levels of low-density lipoprotein (LDL), commonly known as “bad” cholesterol, to levels comparable to those of young rats. This was unexpected because LDL particles are small enough to leave circulation without requiring the microscopic holes in the LSECs.
The study identified a chemical communication mechanism between two types of liver cells to explain these results. The drug activates an enzyme within the endothelial cells that triggers the release of a growth factor known as HB-EGF. This factor sends signals to neighboring liver cells, increasing their capacity to capture and clear both amyloid beta and LDL from the bloodstream.
Future Research Directions
While the results are promising, researchers emphasized that these findings do not yet prove the drug prevents Alzheimer’s or heart disease in humans, as the study was conducted in rats. A reduction of amyloid beta in the blood does not necessarily guarantee a reduction of its accumulation within the brain.