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In a study of older rats, researchers reported that two weeks of cinaciguat treatment restored features of aging liver cells and reduced blood amyloid beta by about 50%. LDL levels also fell to those seen in younger rats, but the results have not been shown in people and do not establish that the drug prevents Alzheimer’s disease or heart disease.
Researchers at the Keck School of Medicine of USC report that an experimental drug, cinaciguat, restored features of aging liver cells in older rats and cut blood levels of amyloid beta by about half after two weeks. The study also found that LDL cholesterol fell to levels measured in younger rats, but the results are limited to animals and do not show that the treatment prevents Alzheimer’s disease or heart disease in humans.
The study, published in the Journal of Biological Chemistry, focused on liver sinusoidal endothelial cells, or LSECs. These cells line small blood vessels in the liver and contain tiny openings that allow substances in the blood to reach neighboring hepatocytes, which process and clear compounds. With age, those openings can shrink or disappear, potentially making it harder for the liver to remove some substances from circulation.
After giving older rats cinaciguat for two weeks, the researchers reported that the LSECs’ structure and function improved and their openings reopened. Blood amyloid beta concentrations fell by approximately 50%, to levels comparable with young rats. Untreated older rats did not show a similar change, according to the report. Amyloid beta is associated with Alzheimer’s disease, but a reduction in its concentration in rat blood is not evidence that the animals had less brain disease or that people would receive the same benefit.
The team also measured low-density lipoprotein (LDL), often called “bad” cholesterol because elevated levels are linked to fatty deposits in arteries. The researchers had not expected LDL to respond: they reasoned that its particles were small enough to leave the bloodstream without passing through the LSEC openings. Instead, LDL in treated older rats fell to levels seen in younger animals. The report describes this as an unexpected finding and a new clue about communication between liver cells, but the supplied findings do not establish the mechanism behind the LDL change.
The findings point to a possible research path that differs from trying to treat Alzheimer’s solely by acting on the brain. The liver filters blood and helps remove compounds from circulation; if age-related changes reduce that capacity, restoring liver function might affect substances associated with disease beyond the liver. The rat results raise that possibility, but they do not show that changing liver function will prevent or treat Alzheimer’s or cardiovascular disease.
The USC report notes that medicines targeting the brain face the challenge of crossing the blood-brain barrier, which limits what can pass from blood into brain tissue. Laurie DeLeve, the study’s corresponding author, said liver-directed treatment could be worth investigating because delivering drugs to the liver may be easier. That is a proposed research rationale, not evidence that cinaciguat is an effective or safe human therapy.
The LDL result may also merit follow-up because it was not the outcome the researchers expected. If further work confirms how the treatment affects LDL, it could help clarify whether the liver-cell changes have broader effects on blood composition. For now, the study supplies an animal finding, not a basis for changing cholesterol or Alzheimer’s care.
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How Aging Changes Liver Filters
The researchers studied liver sinusoidal endothelial cells, specialized cells that form the lining of small vessels within the liver. Their microscopic pores help larger molecules in blood reach hepatocytes, the neighboring cells that perform much of the liver’s processing work. The study’s premise is that age-related loss of these openings can interfere with access to the cells that clear substances.
Amyloid beta is studied in Alzheimer’s research because it can accumulate in the brain and form plaques associated with the disease. The USC researchers examined its levels in the blood, where the liver’s clearance role may matter. A blood measurement, however, does not by itself establish how much amyloid beta is present in the brain or whether a person will develop Alzheimer’s.
The report also places the work against the difficulty of developing brain-targeting Alzheimer’s treatments, citing a high clinical-trial failure rate and the blood-brain barrier as obstacles. The study tests a different idea: improving a function in the liver that could influence what remains in circulation. Its experiments were conducted in rats, so any application to human disease remains a question for further research.
“We need to do further translational work to see whether our findings might point to new therapies.”
— Laurie DeLeve, corresponding author and professor at the Keck School of Medicine of USC
Human Effects Remain Unknown
The reported experiment involved older rats; the source does not describe results in people or establish whether cinaciguat is safe or effective for human use. It is also unclear whether the changes persist after treatment ends, whether they affect amyloid beta in the brain, or whether they alter disease symptoms or long-term outcomes.
The LDL finding needs explanation: the researchers did not expect LDL to change based on their understanding of the LSEC pores, and the supplied report does not provide a full account of the mechanism. The study also does not establish that lowering blood amyloid beta in this way reduces Alzheimer’s risk, or that the LDL change reduces heart disease risk. No human dose, treatment schedule, or clinical benefit is established by these rat findings.
Further Testing Before Human Trials
The next step identified by the study’s corresponding author is translational research to determine whether the results point toward a therapy. Follow-up work would need to test whether the effects can be reproduced, clarify how cinaciguat changes liver-cell function and LDL, and assess safety and durability before researchers could judge whether human studies are appropriate.
Until such evidence is available, the findings should be understood as an early animal study rather than a treatment announcement. The available report does not specify a timeline for additional experiments or clinical trials. Whether restoring aging liver-cell function can change Alzheimer’s or cardiovascular outcomes in people remains unresolved.
Key Questions
What did the researchers find?
In older rats, two weeks of cinaciguat treatment restored features of liver sinusoidal endothelial cells and reduced blood amyloid beta by about 50%. LDL levels also fell to those observed in younger rats.
Does the study show that cinaciguat prevents Alzheimer’s disease?
No. The study reported a change in blood amyloid beta in rats. It did not show that the treatment prevents Alzheimer’s, reduces brain plaques, or benefits people.
Why did the researchers study the liver?
The liver filters blood and helps remove substances from circulation. The researchers investigated whether age-related changes in liver cells might impair that process and whether restoring cell function could change levels of amyloid beta and LDL.
Why was the LDL result unexpected?
The researchers expected little effect on LDL because they thought its particles were small enough to pass out of the bloodstream without using the pores in the liver cells. LDL nevertheless fell in treated rats; the mechanism is not established in the supplied report.
When could this become a treatment for people?
No timeline is given, and the findings have not established a human treatment. Researchers say further translational work is needed before the results can be assessed for possible therapies.
Source: sciencedaily.com
