TL;DR
Get health and wellness essentials delivered free with Prime
- Fast, free delivery on millions of items
- Prime Video, Amazon Music and more included
- Member-only deals all year
In a study of older rats, two weeks of the experimental drug cinaciguat restored features of aging liver sinusoidal endothelial cells and lowered blood amyloid beta by about 50%. LDL levels also returned to those measured in younger rats, but the findings have not been shown in people and do not establish an Alzheimer’s treatment.
Researchers at the Keck School of Medicine of USC report that a two-week course of the experimental drug cinaciguat restored key features of aging liver cells in older rats, while blood levels of amyloid beta fell by about 50%. LDL levels also returned to those measured in younger rats, but the study was conducted in animals and does not show that the drug prevents or treats Alzheimer’s disease or heart disease in humans.
The study, published in the Journal of Biological Chemistry, examined liver sinusoidal endothelial cells, or LSECs. These cells line small blood vessels in the liver and have microscopic openings that allow substances in the blood to pass toward hepatocytes, neighboring cells that perform many of the liver’s processing and removal functions.
As rats age, the openings in LSECs can become smaller or disappear, a change that may interfere with the liver’s ability to clear certain substances. The USC team treated aged rats with cinaciguat for two weeks and compared them with untreated older rats and younger animals. The researchers reported that the drug reopened the cells’ pores and improved their function; untreated older rats did not show a comparable improvement.
After treatment, amyloid beta concentrations in the older rats’ blood were approximately half their previous level and comparable to levels in young rats, according to the report. The researchers also found that LDL concentrations fell to levels seen in younger animals. They had included LDL as a comparison measure and did not expect it to respond: the team reasoned that LDL particles are small enough to leave the bloodstream without passing through the LSEC openings. The unexpected result points to a possible additional effect, but the supplied report does not establish how it occurred.
The findings add to research asking whether organs outside the brain can influence processes associated with Alzheimer’s. The liver filters blood and removes compounds; if age-related changes make that process less effective, restoring liver function could become a different research route from trying to deliver a drug directly into the brain. That route remains a possibility to test, not a demonstrated way to prevent dementia.
The study also connects liver-cell aging with LDL, a measure relevant to cardiovascular risk. Researchers said the LDL result was unexpected, since they did not think the particles depended on the LSEC openings to leave circulation. If further work confirms a mechanism, it could broaden investigation of how liver health relates to blood-borne risk factors. The rat findings alone do not show that cinaciguat reduces artery deposits, heart attacks, Alzheimer’s symptoms, or disease incidence.
USC’s report notes that clinical trials of Alzheimer’s treatments acting directly in the brain have had a high failure rate and that the blood-brain barrier complicates drug delivery. A liver-directed approach might avoid some delivery challenges, but whether cinaciguat can be safely and effectively used in people is not established by this experiment.
Products Worth Considering
Fitbit Versa 2 Health and Fitness Smartwatch with Heart Rate, Alexa, Music, Sleep and Swim Tracking
Fitbit Inspire 3 Health and Fitness Tracker Bundle
Withings BPM Connect Wi-Fi and Bluetooth Blood Pressure Monitor
As an affiliate, we earn on qualifying purchases.
How Aging Changes Liver Filters
LSECs are not ordinary vessel walls: their small openings help connect the bloodstream with hepatocytes. The study focuses on the idea that age-related loss of these openings could hinder access to cells that process substances, including amyloid beta. The researchers tested whether cinaciguat could reverse that change in aged rats.
Amyloid beta is associated with Alzheimer’s disease and can accumulate in the brain, where it is linked to plaques. This experiment measured blood concentrations in rats; it did not establish that reducing amyloid beta in the bloodstream lowered brain plaques or changed behavior or cognition. Likewise, the LDL finding was a blood measurement, not evidence that cardiovascular disease was prevented.
The report describes the work as revealing a previously unknown way liver cells communicate with one another, but the supplied material does not detail that mechanism. It also cites epidemiological findings linking age with Alzheimer’s disease and atherosclerosis, and liver damage with Alzheimer’s risk. Those associations provide motivation for the research, not proof that liver impairment causes either disease.
“We need to do further translational work to see whether our findings might point to new therapies.”
— Laurie DeLeve, corresponding author and USC professor
Human Benefits Remain Unproven
The results so far come from older rats. It is not known whether cinaciguat would restore LSEC function or produce similar changes in amyloid beta and LDL in humans. The report provides no evidence of improved memory, fewer brain plaques, reduced cardiovascular events, or lower risk of developing either disease.
The supplied report does not give the number of animals, treatment dose, detailed effect measurements for LDL, duration of any effect after treatment, or information about adverse effects. Those details matter for judging the strength and safety of the result. The mechanism behind the LDL decline and the newly reported cell-to-cell communication finding also remain unclear from the available account.
There is no reported human trial of cinaciguat for Alzheimer’s disease or heart disease in this material. The findings should not be taken as a recommendation to use the drug or as evidence that changing liver function will prevent either condition.
Further Tests Before Human Trials
DeLeve said the team needs further translational work to determine whether the findings could point to new therapies. Next research would need to test whether the effect can be reproduced, clarify how cinaciguat changes LSEC structure and blood measurements, and assess how long the changes last and whether treatment causes harm.
Studies would also need to establish whether the rat findings apply to people before researchers could assess cinaciguat as a treatment strategy. Until such evidence is available, the main confirmed development is a short-term result in aged rats: restored liver-cell features alongside lower blood amyloid beta and LDL. Whether those changes translate into clinical benefits remains unknown.
Key Questions
What did the researchers find?
In older rats, two weeks of cinaciguat treatment restored features of liver sinusoidal endothelial cells. The team reported that blood amyloid beta fell by about 50% and LDL reached levels measured in younger rats.
Does the study show that cinaciguat treats Alzheimer’s disease?
No. The study measured blood markers in rats. It did not test people or show changes in brain plaques, memory, Alzheimer’s symptoms, or disease risk.
Why did researchers study the liver?
The liver filters blood, and the team investigated whether age-related changes in its endothelial cells could make it harder to clear substances such as amyloid beta. The study explores a possible route for future research, not a proven treatment approach.
What remains unknown about the findings?
It is not yet clear whether the effects occur in humans, how long they last, what explains the LDL change, or what risks treatment might carry. The supplied report also does not provide detailed animal counts or dosing information.
Source: sciencedaily.com
