Lead author of the study Hongjun “Harry” Fu, PhD, professor of neuroscience at Ohio State, recalls that each year around the world, approximately 2.5 million people suffer traumatic brain injuries and confirms with this study that risk factor for Alzheimer’s disease later in life. “Given the high prevalence and prevalence of traumatic brain injury and Alzheimer’s disease, it is essential to
understand the molecular mechanism underlying the transition from head injury to Alzheimer’s disease
in order to develop therapies that can prevent this risk.”
The study is carried out both in vitro, on post-mortem human brain tissue and in vivo on mouse models of brain injury, to study these molecular foundations involved in the risk of Alzheimer’s disease after head trauma. These analyzes show that:
- head trauma increases levels of hyperphosphorylated tau protein;
- activates astro- and microgliosis, induces synaptic dysfunction;
- what induces cognitive disorders linked to the development of Alzheimer’s disease;
- the negative regulation of a protein involved in the clearance of proteins by the autophagy-lysosome pathway (BAG3) also contributes to the accumulation of toxic tau in neurons and oligodendrocytes, after head trauma: the demonstration is provided here in the both in mouse models and human postmortem brain tissue with a history of head trauma;
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BAG3 overexpression accelerates tau hyperphosphorylation, increases synaptic dysfunction and cognitive deficits.
A new therapeutic target? Targeting BAG3 in neurons appears to be a promising strategy to prevent or reduce Alzheimer’s disease-like pathology.
“Since previous research using human tissue and animal models has also suggested that tau pathology increases after head trauma, we believe that BAG3 may be one of the contributing factors to this development.”
Research continues to validate the relationship between head trauma, BAG3, tau pathology, gliosis and neurodegeneration and to understand how brain trauma and Alzheimer’s disease are therefore biologically linked.
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