Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease identified by the unusual accumulation of hyperphosphorylated tau protein in the brain. Currently, similar to many neurodegenerative conditions, Define Diagnosis of CTE can only be definitively achieved through a post-mortem examination of brain tissue. In a significant step towards refining diagnostic accuracy, a consensus panel of neuropathologists convened to establish neuropathological criteria for CTE. This panel, supported by the NINDS/NIBIB, undertook a blind evaluation of 25 cases encompassing various tauopathies, including CTE, Alzheimer’s disease, and other related conditions, to improve diagnostic consistency.
The study revealed a strong level of agreement among the expert neuropathologists in their assessments, achieving a Cohen’s kappa of 0.67 across all cases and an even higher agreement of 0.78 specifically for CTE diagnosis. Based on these findings, the panel formally define diagnosis of the pathognomonic lesion of CTE as the accumulation of abnormal hyperphosphorylated tau (p-tau). This accumulation is specifically located in neurons and astroglia around small blood vessels, predominantly at the depths of cortical sulci and in an irregular distribution pattern.
In addition to the pathognomonic lesion, the panel also define diagnosis of several supportive, though non-specific, p-tau-immunoreactive features that are indicative of CTE. These include:
- Pretangles and neurofibrillary tangles (NFTs) affecting the superficial layers (layers II-III) of the cerebral cortex.
- Pretangles, NFTs, or extracellular tangles in the CA2 region, and pretangles along with proximal dendritic swellings in the CA4 region of the hippocampus.
- Neuronal and astrocytic aggregates within subcortical nuclei.
- Thorn-shaped astrocytes located at the glial limitans of the subpial and periventricular regions.
- Large grain-like and dot-like structures.
Furthermore, the panel noted supportive non-p-tau pathologies, such as TDP-43 immunoreactive neuronal cytoplasmic inclusions and dot-like structures, particularly in the hippocampus, anteromedial temporal cortex, and amygdala. For standardized pathological evaluation, the consensus group recommended a minimum protocol for tissue blocking and staining. They also emphasized several areas for future research to further refine and validate these initial diagnostic criteria.
This collaborative study marks a crucial first step in establishing validated neuropathological criteria to define diagnosis of CTE. These defined criteria are essential for advancing both clinical and mechanistic research into CTE, paving the way for more accurate diagnosis and a deeper understanding of this complex neurodegenerative condition.
