CONNECT-TBI

Background

In the past several decades, there has been increasing awareness of the neuropathological effects of traumatic brain injury (TBI) and their relation to increased risk of a range of neurodegenerative diseases, including Alzheimer’s disease (AD) and AD-related dementias (AD/ADRD).

Intense media attention has focused on the association of repetitive mild TBI within contact sports and increased risk of the specific neurodegenerative pathology of chronic traumatic encephalopathy (CTE). Unfortunately, there has been comparatively little attention paid to the complex of neurodegenerative pathologies arising after exposure to TBI across the full spectrum of injury mechanisms and severities; a complex of pathologies we consider under the more encompassing term, TBI-related neurodegeneration (TReND). Further, few studies have examined TReND and its relation to the pathologies of aging and wider neurodegeneration, in particular the already characterized pathologies recognized as AD/ADRD. Arguably the greatest barrier to progress in this field has been the limited number of suitable human brain tissue samples available to support research in outcomes from TBI.

To overcome this, the COllaborative Neuropathology NEtwork Characterizing ouTcomes of TBI (CONNECT-TBI), will bring together unique tissue resources in TBI and AD/ADRD, together with 26 leading investigators from 12 institutions to generate an unparalleled, comprehensive neuropathological and clinical data resource. Leveraging these resources, CONNECT-TBI will conduct a comprehensive research
effort characterizing the spectrum of pathologies arising in late survivors of all types and severities of TBI.

Aims of CONNECT-TBI

Aim 1: To establish a comprehensive tissue resource in the research of Traumatic Brain Injury (TBI) comprising both existing materials and prospective case material from patients across a wide range of injury subtypes and survivals, including:

  • former athletes across multiple global sports
  • long-term survivors of mild, moderate, or severe TBI
  • former military personnel exposed to blast and non-blast TBI
  • multiple international, prospective studies in TBI

Aim 2: To characterise the extent, distribution and range of neuropathologies that result following exposure to all types and severities of TBI and consider the influence of injury type and survival interval on chronic TBI pathology

Aim 3: To describe the association between extent, distribution and phenotype of cTBI neuropathology in context with clinical presentation

Aim 4: To contrast cTBI neuropathology to that of aging and wider neurodegenerative disease, including Alzheimer’s and Parkinson’s/Lewy body disease and related neurodegenerative disorders and establish prevalence of cTBI pathology in patients with neurodegenerative disease.

Aim 5: Under CONNECT-TBI, develop a networked archive of biospecimens linked to comprehensive clinical and neuropathological data representing a central point of access to unique tissue resources to support research for broader TBI research community

Why is our work important?

In a nutshell our work is directed towards understanding how brain injuries might lead to lifelong degenerative brain disease, including dementia, in some people. At some point we and others working in this field would hope that we can understand why this might happen, how to detect it in life and, most importantly, how we might prevent or treat it.

In little more than a decade the term “Chronic Traumatic Encephalopathy” (CTE) has emerged into public consciousness via intense media coverage, medical television dramas, and even a Hollywood movie starring Will Smith (Concussion, 2015, Columbia Pictures)¹. While this attention has raised public awareness of an important public health concern regarding the late effects of Traumatic Brain Injury (TBI), it has also often included inaccurate or confusing descriptions of the fundamental aspects of CTE in particular.

In contrast to general impressions, the actual incidence of CTE remains unknown and current consensus of neuropathological criteria are acknowledged as only “preliminary”² in part recognition that these criteria are founded on examination of a limited number of selected cases.

The narrow focus on CTE in the public consciousness has occurred at the expense of developing a more open minded and inclusive determination of the many other progressive neuropathological changes and clinical features of both repetitive mild and single severe TBI 3-5. CONNECT-TBI is working to investigate and characterise all neurodegenerative changes after TBI under the umbrella concept of “TBI-Related NeuroDegeneration (TReND)” to compare and contrast potentially distinct neuropathological and clinical features between types of TBI in comparison with other neurodegenerative disorders.

 

 

References

¹ Concussion, Landesman, L. (Columbia Pictures, 2015).
² McKee, A. C. et al. The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta Neuropathol 131, 75-86, doi:10.1007/s00401-015-1515-z
(2016) 
³ Smith, D. H., Johnson, V. E. & Stewart, W. Chronic neuropathologies of single and repetitive TBI: substrates of dementia? Nat Rev Neurol 9, 211-221, doi: 10.1038/nrneurol.2013.29 (2013)