mRNA and protein levels of fibrinogen chains are differentially expressed in mouse brain microvessels with aging and are present in the cerebral cortex of adult rhesus macaques

Background: Fibrinogen (Fgn) in the brain and cerebral blood vessels are linked to neuroinflammation and Alzheimer’s disease. Recently, we reported that Fgn-beta protein expression was significantly higher in old vs. young mouse brain microvessels (MVs: end-arterioles, capillaries, and venules), and elevated Fgn leads to endothelial and blood-brain barrier dysfunction in primary human brain microvascular endothelial cells (BMECs). To examine regulation of Fgn production, we investigated the intrinsic abundance of mRNA and protein of individual Fgn chains in mouse brain MVs, cerebral cortex of rhesus macaques, and human brain MV-specific primary cells. Methods: Proteomics, western blot, and RT-qPCR (SYBR Green) analyses were performed to compare age-, sex-, and species- specific expression of mRNA and protein levels of Fgn-alpha (FGA), -beta (FGB), and -gamma (FGG) chains in brain MVs isolated from young (4–6 months) and old (20–21 months) mice, from adult rhesus macaques' brain tissues, and from human-derived BMECs and astrocytes. Results: Proteomic analysis showed a significant age-related increase in FGB, but not FGA or FGG proteins, in brain MVs of aged compared with young mice (n = 6/group), a finding corroborated by western blotting. In young mouse proteome, the abundance of FGG (p < 0.05) was higher in female vs. male mice (n = 3/group). However, in the old mouse proteome, the abundance of FGA and FGB (both p < 0.05) was higher in male than in female mice (n = 3/group). In the adult macaque brain cortex, FGA protein was detected in one male (n = 2) and one female (n = 3); however, a high abundance of FGB and FGG proteins was observed for both sexes. RT-qPCR of brain MVs showed no detectable FGA mRNA in either age group; however, FGB mRNA was detected in 4 young and 6 old mice (n = 10/group). FGG isotype 1 (FGG1) mRNA in brain MVs was detected in 6 of 10 young and all 10 old mice, which was significantly higher in old compared with young mice (p < 0.05). FGG isotype 2 (FGG2) was the most abundant mRNA detected in all young and old mice brain MVs (n = 10/group), showing no significant age-specific differences. Notably, FGA, FGB, and FGG1 mRNA were detected in early passaged primary human BMECs and astrocytes, but subsequent passaged cells failed to show mRNA for any chain. Conclusion: Our findings challenge the dogma that Fgn production is mainly a product of hepatocytes. The intrinsic abundance of mRNA and protein of individual Fgn chains in the brain and brain vasculature may reflect normal physiology, yet this abundance could become detrimental with aging or other neuropathological challenges. Funding support: NIH grants: R01NS136041(PKC), R56AG075988 (DWB), R01AG083567 (IR-G), R21/R33AI110158 (SEB), and P51OD011104 (TNPRC). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.