Summary
A bioRxiv preprint reports higher Serpin A3 levels in human brain tissue from cases with cerebral amyloid angiopathy and Alzheimer’s disease than in neurological controls. The protein was also prominent around damaged vessels in one postmortem case of severe lecanemab-associated ARIA.
A bioRxiv preprint reports higher levels of the protein Serpin A3 in human brain tissue from cases with cerebral amyloid angiopathy (CAA) and Alzheimer’s disease than in neurological controls. In a separate postmortem case of active, severe amyloid-related imaging abnormalities (ARIA) associated with lecanemab, the researchers found prominent Serpin A3 around inflamed, dilated blood vessels and microhemorrhages.
The study combined analyses of single-nucleus transcriptomic datasets with protein measurements and two- and three-dimensional microscopy of human brain tissue. Its findings point to Serpin A3 as a marker associated with vascular injury and reactive astrocytes, rather than establishing that the protein causes the damage.
Serpin A3 clustered around affected vessels
Serpin A3 is known as a marker of reactive astrocytes—support cells in the brain that change their activity in response to injury or disease. In the tissue examined, its distribution varied, but the protein was found predominantly in astrocytes associated with degenerating arterioles. The researchers also detected it around amyloid plaques within brain tissue.
CAA involves amyloid accumulation in the walls of brain blood vessels. The preprint reports increased Serpin A3 protein in CAA and Alzheimer’s disease cases compared with neurological controls, based on western blotting and quantitative microscopy. The abstract does not provide the group sizes or numerical effect estimates, so the size of the reported differences cannot be assessed from the summary alone.
The ARIA finding comes from one postmortem case
The researchers used light-sheet microscopy to examine a postmortem case of active, severe lecanemab-associated ARIA. Serpin A3 staining was prominent around inflamed, dilated vessels and microhemorrhages; levels in this case were reported as higher than those in the CAA cases.
That observation adds a detailed view of Serpin A3 in tissue affected by a serious vascular event, but it is based on a single case. Across the study, tissue associations show where the protein is present; they cannot determine whether Serpin A3 contributes to vascular injury or is produced in response to it. The findings are reported in a bioRxiv preprint.