Brain vascular basement membrane: Comparison of human and mouse brain at the transcriptomic and proteomic levels

The cerebrovascular basement membrane (BM) is a key component of the blood-brain barrier (BBB). The BM provides structural support for brain microvascular endothelial cells and the supporting cells of the neurovascular unit, and facilitates cell signaling through adhesion receptors, regulates the concentration of soluble factors, and serves as an additional barrier for transport. However, our understanding of the composition of BM remains incomplete. Here we analyze recent proteomic and genomic data to assess the composition of BM in human and mouse brain, and in tissue-engineered BBB models. All data sets confirm that the main components of brain BM are collagen IV a1/2 and laminin, along with agrin, perlecan, and nidogen. Transcriptomic data from human BMECs suggests that the main laminin isoform is Laminin 321, while transcriptomic data from mice and proteomic data from mice and humans suggest that Laminin 521 is the predominant isoform. Transcriptomic data from iBMECs suggest that Laminin 511 is the predominant isoform. The supporting molecules agrin, perlecan, and nidogen were detected at significant levels in all studies, although only nidogen 1 was detected in the human transcriptomic data sets. No significant differences in human BM composition were observed in BMECs along the arterio-venous axis, or in comparison of healthy and AD brains.