Many MindedOld rats' livers clear more LDL and amyloid-beta after two weeks of an experimental drug
A University of Southern California team that includes liver researcher Sam de Leve tested the experimental drug cinaciguat in aging rats. Two-year-old rats received it daily for two weeks and were compared with untreated old rats and four-month-old rats. Blood amyloid-beta 40, a protein linked to Alzheimer's, fell by half in the treated old rats, to youthful levels. LDL cholesterol also dropped. The results appear in the Journal of Biological Chemistry.
The treatment reopened the small openings in the cells that line liver blood vessels, which shrink and become fewer with age. But LDL particles are small enough to cross that lining anyway, so the openings could not explain the LDL drop. The team's cell experiments pointed to a signal instead. Fluid from young vessel-lining cells helped young-rat liver cells take up LDL, while fluid from old cells did no better than ordinary medium. Old cells made the precursor of the growth factor HB-EGF but released no detectable soluble amounts, and cinaciguat restored release. Adding HB-EGF directly improved liver-cell uptake of LDL and amyloid-beta. Two capture proteins sat at lower levels on the old cells' surface despite similar total amounts, and treatment restored surface levels.
Why it matters: if aging blunts the liver's ability to clear these molecules, restoring that function is a possible route to lowering both, using a lever outside the brain. That would be a different kind of preventive health tool.
The caveats are large. The rats were healthy and aging, not an Alzheimer's model. The study did not show fewer brain plaques, better memory or prevention of the disease, and it is unknown whether better liver clearance protects the brain. The researchers did not directly establish that HB-EGF causes the surface-protein change, and experiments used three to six independent biological samples per condition. The next step is an Alzheimer's animal model; human use needs more work on effectiveness and the safety of related drugs.
Source: ScienceAlert