Even though Alzheimer’s disease, the hereditary vascular disorder CADASIL, and traumatic brain injury are all associated with inflammation and changes in the brain’s blood vessels, many vascular cells appear to retain their normal genetic programmes during disease, reports a study from Karolinska Institutet published in Nature Communications. Researchers also identified a possible explanation why traumatic brain injuries may raise the risk of developing neurodegenerative diseases.
Researchers have long sought to understand how the brain’s blood vessels are affected by neurological diseases. In the current study, more than 250,000 individual cells from mouse models of Alzheimer’s disease, CADASIL, and traumatic brain injury were analysed. By mapping which genes were active in different cell types, researchers were able to compare how vascular cells and immune cells responded during disease progression. They also identified two previously undefined types of vascular cells in the brain, contributing to a more detailed map of the brain’s vascular system.
Brain blood vessels more resilient than previously thought
The analysis showed that most vascular cells in the brain underwent surprisingly few changes, despite extensive disease-related alterations in brain tissue.
Photo: Stefan Zimmerman
“We were surprised by how stable the gene expression patterns of vascular cells were across all disease models. The results suggest that the brain’s blood vessels may be more resilient to disease-related changes in brain tissue than previously believed,” says Michael Vanlandewijck , researcher at the Department of Medicine, Huddinge , Karolinska Institutet.
Michael Vanlandewijck led the study together with KI researchers Per Nilsson , Helena Karlström , and Eric Thelin .
Understanding the increased risk of neurodegenerative diseases
In contrast to the vascular cells, microglia, the brain’s resident immune cells, responded strongly, and the researchers observed that different diseases gave rise to distinct gene expression patterns in microglia.
The study also showed that, following traumatic brain injury, microglia gradually began to resemble those observed in Alzheimer’s disease. These similarities became more pronounced over time after the injury.
“This may help explain why individuals who have suffered a traumatic brain injury are at increased risk of developing neurodegenerative symptoms later in life,” says Michael Vanlandewijck.
The study was conducted in collaboration between researchers at Karolinska Institutet, Uppsala University, and several other research centres across Europe. The research was funded by, among others, the Swedish Brain Foundation (Hjärnfonden), the Alzheimer Foundation Sweden (Alzheimerfonden), the Swedish Research Council, Karolinska Institutet, the Leif Lundblad Foundation, and Region Stockholm.
Publication
Bjørnholm KD, Li H, Del Gaudio F, Mocci G, Shao W, Baldisseri E, Rao SB, Lindblad C, Fletcher-Sandersjöö A, Vázquez-Liébanas E, Pietilä R, Muhl L, Jiang R, Kalantzi C, Cheung J, Jin S, Svensson M, Lesnik Oberstein SAJ, Syvänen S, Mäe MA, Torp R, Lendahl U, Karlström H, Thelin EP, Nilsson P, Vanlandewijck M. Nature Communications, 16 July 2026, doi: 10.1038/s41467-026-75367-0.
