After age and genetic risk factors, traumatic brain injury is the third leading cause of Alzheimer's disease (AD). Resulting from blows to the head, traumatic brain injury (TBI) can have long-lasting effects on the structure and function of the brain. On 13 April, a team of researchers led by Prof. Andrew Pieper published a paper in the Cell journal, describing how TBI can induce changes in Tau proteins that damage brain cells, potentially leading to the development of AD and other neurodegenerative diseases in later life.
Tangled tau proteins are known as a pathological hallmark of AD, damaging nerve cells in the brain and contributing to cognitive decline. Using animal models of TBI, Prof. Pieper and colleagues observed the rapid accumulation of ac-Tau, a specialised form of the protein, after brain injury. Ac-Tau could be measured in the blood of TBI animals, and was associated with neurodegeneration and cognitive impairment, suggesting that it could be a helpful biomarker in this context. Treatment of animals with drugs such as salsalate (a non-steroidal anti-inflammatory drug/NSAID) was able to prevent ac-Tau accumulation after TBI.
To check whether ac-tau could also be relevant for TBI and AD in humans, the researchers then tested a small number of postmortem brain samples from donors with AD who had also experienced TBI. Similar to what they observed in animal models, they saw an increased presence of ac-Tau in brain samples from donors with AD and a history of TBI. Using a large database of US health records, including data from over 7 million insured individuals, the researchers assessed whether the use of salsalate or diflunisal (two NSAIDs with a different mode of action to aspirin) was associated with fewer TBI and/or AD diagnoses. These data analyses revealed that people taking salsalate were 30% less likely to have a clinical diagnosis of TBI, compared to people taking aspirin. They also observed a reduced incidence of AD in people taking salsalate or diflunisal compared to those prescribed aspirin, even when correcting for known AD risk factors such as diabetes, hypertension and heart disease.
https://www.sciencedirect.com/science/article/pii/S0092867421003639
