An increased risk of dementia in persons exposed to brain trauma, traumatic brain injury, has been known for almost a century. Yet we know very little about the molecular causes behind this, making it difficult to find effective treatments to prevent the development of dementia affected by traumatic brain injury. A research team of the Strategic Research Area Multipark, but Lund University argues that the blood vessels in the brain have the keys to future therapies.
Brain trauma usually damages cerebral blood flow, possibly due to pathological changes in the vascular smooth muscle cells in the vascular wall. These blood flow disorders can lead to secondary brain injury, which deteriorates the damage to the brain, although it remains unknown how exactly this happens.
To bridge this gap, Niklas Marklund, professor at Lund University and Neurosurgical Consultant of the Skåne University Hospital, together with the experimental scientist Ilknur Özen to take a deeper look in the molecular details. In collaboration with Uppsala University, they investigated brain tissue from 15 patients, surgically removed due to bleeding and swelling within a week of their traumatic brain injury. They discovered that the changes in the vascular smooth muscle cells coincide with increased aggregation of amyloid-beta, a protein linked to Alzheimer’s disease.
We were surprised to see that even young patients showed this accumulation of amyloid beta together with the vascular changes caused by the brain trauma. “
Ilknur Özen, first author of the study
She continues: “Our findings suggest that vascular changes can be more important for neurodegeneration than previously thought.”
Niklas Marklund adds: “This challenges the existing paradigm in neurodegeneration-related diseases by indicating that vascular dysfunction could be an early event that causes the progression of amyloid-related diseases rather than being caused by neuronal damage. “
Although aging leads to functional changes in the vascular system, brain trauma can even aggravate and accelerate these processes in younger patients. Nevertheless, far from everyone affected by brain trauma develops Alzheimer’s disease. That is why more research is needed.
“We are not there yet, but hopefully, increased knowledge about what will open at the molecular level in the blood vessel cells after brain trauma after the brain trauma will open possibilities for new treatments,” concludes Niklas Marklund.
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Journal Reference:
Özen, I., et Alt Alto. (2025). Traumatic brain injury causes early aggregation of beta-amyloid peptides and notch3 reduction in vascular smooth muscle cells from leptominingal arteries. Acta Neuropathologic. doi.org/10.1007/s00401-025-02848-9.