The Blood Brain Barrier

Maintaining the brain's delicate internal environment is essential for proper function in everyday tasks. The blood-brain barrier (BBB) serves as a filter, allowing essential molecules into the brain while keeping harmful ones out. When there is injury to the BBB, damaging substances like toxins can get through to brain tissue, causing inflammation and injury. Traumatic brain injury (TBI) is one of the processes that may allow such a breakdown of protection. In a paper by researchers from Stanford University, they examined how the blood-brain barrier may mediate development of Alzheimer’s disease (AD) after TBI, with the hopes of outlining the targets for future AD prevention treatments. 

Accumulation of proteins amyloid-beta and tau has been identified as one of the mechanisms by which AD can develop. Another process involves vascular abnormalities, which may be caused by reduced cerebral blood flow or by disruption to the BBB itself. Because breakdown of the blood-brain barrier is a shared mechanism between TBI and AD, it has led researchers to believe that the two may be connected through this process. Disruption of the BBB may be seen in both the acute and chronic phases of TBI, possibly contributing to other chronic diseases like AD. The BBB believed is believed to help clear the brain of amyloid beta, supporting the idea that preventing BBB damage can slow the development of AD. Additionally, chronic neuroinflammation, another factor thought to contribute to AD, may be prevented by protecting the BBB from damage.  

Research into TBI, AD, and the blood-brain barrier has also suggested that pharmacologic repair to the BBB after TBI might prevent neurodegeneration. Such a finding makes a strong case for the development of drug treatments for BBB repair as a method of mediating AD progression. A drug meant to target and preserve the BBB has not yet reached clinical trials, as the exact mechanisms of the blood-brain barrier are still largely unknown, especially  the processes that mediate its damage. Determining which molecular mechanisms are involved in this process is essential to designing methods to preserve its integrity. 

Despite the current findings that suggest a connection between TBI and AD through the BBB, there is much to be discovered about the processes through which this connection exists. Future research into how damage to the blood-brain barrier occurs and how it contributes to AD will allow development of therapies targeting the blood-brain barrier, potentially slowing neurodegeneration in those who have experienced TBI,  a big step forward in sustaining long-term cognitive function. 

Article of Interest:

Sun B, Li L, Harris OA, Luo J. Blood-brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease. Transl Neurodegener. 2025;14(1):16. Published 2025 Mar 26. doi:10.1186/s40035-025-00478-5