CENC0005C - Tau Modifications Study

The continued increase in the use of improvised explosive devices (IEDs) and the protection provided by modern body armor places mild traumatic brain injury (mTBI, also referred to as concussion) as the “signature injury” of modern warfare. The consequences of mTBI may persist indefinitely in Veterans, causing progressive neurological degeneration similar to Alzheimer’s disease. Unfortunately, little is known about its acute effects on the brain or its long-term behavioral consequences, particularly in individuals who have suffered multiple mTBIs. With the current practice of repeated redeployment, the opportunities for Service members to experience multiple mTBIs increase dramatically. A single mTBI is usually perceived as relatively benign because most people recover quickly and fully without any lingering symptoms; however, in those affected, some symptoms appear right away, while others progress over days or months. Indeed, mTBI can silently affect a subject without inducing obvious behavioral changes. Although there are many procedures to assist the physician in the detection of mTBI, very little is known about the underlying pathobiology of neuronal degeneration in patients with mTBI.

tau study images

One of the few known biological changes seen in mTBI is the massive intraneuronal accumulation of a protein called Tau in very specific and recognizable patterns in the human brain. The consequences of repeated mTBI (r-mTBI) over a prolonged period have not been well studied, and the factors and mechanisms that contribute to the long-term consequences of r-mTBI are still poorly understood.

Thus the goal of this study is to develop an animal model of r-mTBI model that will allow the tracking of progressive intraneuronal tau alterations that can be correlated with behavioral dysfunction, fluorescent in situ hybridization, and gene expression signatures. The model could then be used to assess the effects of interventions. The observations made in the animal model will be tested for agreement in soldiers who have died after sustaining r-mTBI. Exploitation of such a model will have great translational significance by providing seminal data needed to develop new and better treatments for our military personnel with mTBI.

At a Glance

Study type:

Basic science animal study

Objective:

To develop an animal model of tau accumulation and behavioral changes in mTBI mice

Population:

Transgenic mice which express human tau exposed to mild TBI

Number of participants:

672 mice

Data collection:

Data collection will include animal behavioral assays, veterinary practice data, protein quantification, Stereological immunohistochemical images, Immunofluorescence confocal images, and gene expression microarray data.

Participating sites:

Barrow Neurological Foundation, Roskamp Institute, RTI International

Principal investigator:

Elliot Mufson, Ph.D., Barrow Neurological Institute 

Duration:

5 years