Does the Liver Hold the Secret to Preventing Alzheimer's? Study Reveals a Surprise

The brain may not be the sole key to combating Alzheimer’s disease, as a new scientific study suggests that the liver may play an unexpected role in reducing the accumulation of substances linked to brain and heart diseases with aging.

Researchers at the Keck School of Medicine of the University of Southern California (USC) found that an experimental drug called Cinaciguat was able to restore some functions of aged liver cells in rats, leading to a 50% reduction in levels of amyloid beta protein associated with Alzheimer’s, and bringing harmful cholesterol levels back to those seen in young animals.

The findings were published in the Journal of Biological Chemistry, potentially opening the door to a new therapeutic strategy targeting the liver rather than attempting to deliver drugs directly to the brain.

The liver plays a crucial role in purifying blood and eliminating substances that can become harmful if they accumulate in the body, including amyloid beta protein, which is linked to the formation of plaques in the brains of Alzheimer’s patients.

With aging, the liver’s efficiency in clearing these substances declines, prompting researchers to investigate whether restoring its normal functions could help reduce their accumulation.

This approach gains additional significance due to the difficulty of developing treatments that target the brain directly, as the blood-brain barrier prevents many substances and drugs from reaching it, representing one of the main challenges in developing effective Alzheimer’s treatments.

The researchers focused on a specialized type of cell known as hepatic sinusoidal endothelial cells, which line the tiny blood vessels within the liver and contain microscopic pores that allow molecules to pass from the blood into liver cells responsible for processing and eliminating substances.

However, these pores gradually narrow or disappear with aging, weakening the liver’s ability to purify blood. To test whether these changes could be reversed, the scientists administered Cinaciguat to aged rats for two weeks, then compared the results with untreated aged rats and young rats.

The results showed that the treatment improved the structure and function of endothelial cells and helped restore their microscopic pores, coinciding with a halving of amyloid beta levels in the blood, bringing them closer to levels recorded in young animals.

The findings did not stop at amyloid beta protein; researchers also observed a decrease in low-density lipoprotein (LDL) protein, known as harmful cholesterol, in the treated rats, returning to levels seen in young animals.

This discovery was surprising, as LDL cholesterol molecules can leave the bloodstream without needing to pass through the microscopic pores of hepatic sinusoidal endothelial cells.

Further analysis revealed a chemical communication mechanism between two types of liver cells: the drug activates an enzyme within endothelial cells, which stimulates the release of a growth factor known as HB-EGF, which in turn sends signals to adjacent liver cells.

These signals help liver cells increase their ability to capture and eliminate amyloid beta and LDL cholesterol from the blood.

Researchers believe the results identify a promising therapeutic pathway based on restoring the liver’s ability to purify blood, rather than focusing exclusively on targeting the brain.

However, these findings do not mean that the drug prevents Alzheimer’s or treats heart disease. The experiment was conducted on rats, and it remains necessary to verify its efficacy and safety in humans.

The research team plans to conduct further experiments to determine whether the restoration of liver function actually translates into brain protection against the disease, and whether the discovered mechanism can be leveraged to develop future treatments for cardiovascular diseases. The study offers a new perspective on aging research, suggesting that brain and heart protection may begin in another organ—the liver—but translating this discovery into a treatment available to humans still requires further research.